Propofol promotes apoptosis of colorectal cancer cells via alleviating the suppression of lncRNA HOXA11-AS on miRNA let-7i

2020 ◽  
Vol 98 (2) ◽  
pp. 90-98 ◽  
Author(s):  
Yan-Ling Ren ◽  
Wei Zhang
Keyword(s):  
Colorectal Cancer ◽  
Caspase 3 ◽  
Cell Counting ◽  
Loss Of Function ◽  
Anaesthetic Agents ◽  
Colorectal Cancer Cells ◽  
Intravenous Anaesthetic ◽  
A Cell ◽  
Underlying Mechanisms ◽  
Sw620 Cells

To date, surgical resection is the mainstay for the treatment of colorectal cancer (CRC). Propofol (2,6-diisopropylphenol), one of the most commonly used intravenous anaesthetic agents, has been reported to be involved in modulating the malignancy of a variety of human cancers. However, the underlying mechanisms remain poorly understood. In this study, using a cell counting kit (CCK-8), flow cytometry, and caspase-3 cleavage assays, we found that propofol promoted cell apoptosis and inhibited cell proliferation in both Colo205 and SW620 cells, through the down-regulation of HOXA11-AS and up-regulation of let-7i. Moreover, gain-of-function studies of HOXA11-AS or loss-of-function studies of let-7i also revealed a negative correlation between HOXA11-AS and let-7i in propofol-mediated biological functions of CRC cells. Furthermore, our mechanistic experiments revealed that HOXA11-AS acts as a molecular sponge for let-7i, thereby regulating the expression of ABCC10. We investigate the theory that propofol suppresses colorectal cancer tumorigenesis by modulating the HOXA11-AS–let-7i–ABCC10 regulatory network, indicating the potential for propofol to control CRC development.

scholarly journals Coptidis Rhizoma Extract Reverses 5-Fluorouracil Resistance in hct116 Human Colorectal Cancer Cells via Modulation of Thymidylate Synthase

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 1856
Author(s):  
Yong-Hwi Kang ◽  
Jin-Seok Lee ◽  
Nam-Hun Lee ◽  
Seung-Hyung Kim ◽  
Chang-Seob Seo ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Thymidylate Synthase ◽  
Cell Cycle Distribution ◽  
Human Colorectal Cancer ◽  
Common Cancer ◽  
G1 Phase Arrest ◽  
Colorectal Cancer Cells ◽  
Coptidis Rhizoma ◽  
Underlying Mechanisms ◽  
Human Colorectal Cancer Cells

Colorectal cancer (CRC) is a malignancy of the colon or rectum. It is ranked as the third most common cancer in both men and women worldwide. Early resection permitted by early detection is the best treatment, and chemotherapy is another main treatment, particularly for patients with advanced CRC. A well-known thymidylate synthase (TS) inhibitor, 5-fluorouracil (5-FU), is frequently prescribed to CRC patients; however, drug resistance is a critical limitation of its clinical application. Based on the hypothesis that Coptidis Rhizoma extract (CRE) can abolish this 5-FU resistance, we explored the efficacy and underlying mechanisms of CRE in 5-FU-resistant (HCT116/R) and parental HCT116 (HCT116/WT) cells. Compared to treatment with 5-FU alone, combination treatment with CRE and 5-FU drastically reduced the viability of HCT116/R cells. The cell cycle distribution assay showed significant induction of the G0/G1 phase arrest by co-treatment with CRE and 5-FU. In addition, the combination of CRE and 5-FU notably suppressed the activity of TS, which was overexpressed in HCT116/R cells, as compared to HCT116/WT cells. Our findings support the potential of CRE as an adjuvant agent against 5-FU-resistant colorectal cancers and indicate that the underlying mechanisms might involve inhibition of TS expression.

scholarly journals Calcium Channel Protein ORAI1 Mediates TGF-β Induced Epithelial-to-Mesenchymal Transition in Colorectal Cancer Cells

2021 ◽  
Vol 11 ◽  
Author(s):  
Qingjie Kang ◽  
Xudong Peng ◽  
Xiangshu Li ◽  
Denghua Hu ◽  
Guangxu Wen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Migration ◽  
Calcium Channel ◽  
Cancer Cells ◽  
Transforming Growth Factor ◽  
Mesenchymal Transition ◽  
Colorectal Cancer Cells ◽  
Sw480 Cells ◽  
Sw620 Cells ◽  
Tgf Β1

Accumulating evidence suggested that calcium release-activated calcium modulator 1(ORAI1), a key calcium channel pore-forming protein-mediated store-operated Ca2+ entry (SOCE), is associated with human cancer. However, its role in colorectal cancer (CRC) progression has not been well studied. Epithelial-mesenchymal transition (EMT) is a multistep process that occurs during the progression of cancers and is necessary for metastasis of epithelial cancer. Transforming growth factor-β (TGF-β) is a pleiotropic cytokine that has been shown to induce EMT. In this study, we are aimed at exploring the effects of ORAI1 on TGF-β1-induced EMT process in CRC cells. Herein, we confirmed ORAI1 expression was higher in CRC tissues than in adjacent non-cancerous tissues by using immunohistochemical staining and Western blot analysis. Higher ORAI1 expression was associated with more advanced clinical stage, higher incidence of metastasis and shorter overall survival. We compared ORAI1 expression in SW480 and SW620 cells, two CRC cell lines with the same genetic background, but different metastatic potential. We found ORAI1 expression was significantly higher in SW620 cells which exhibited higher EMT characteristics. Furthermore, knockdown of ORAI1 suppressed the EMT of SW620 Cells. After induced the EMT process in SW480 cells with TGF-β1, we found treatment of TGF-β1 showed a significant increase in cell migration along with the loss of E-cadherin and an increase in N-cadherin and Vimentin protein levels. Also, TGF-β1 treatment increased ORAI1 expression and was closely associated with the increase of SOCE. Silencing ORAI1 significantly suppressed Ca2+ entry, reversed the changes of EMT-relevant marks expression induced by TGF-β1, and inhibited TGF-β1-mediated calpain activation and cell migration. Finally, we blocked SOCE with 2-APB (2-Aminoethyl diphenylborinate), a pharmacological inhibitor. Interestingly, 2-APB and sh-ORAI1 both exhibited similar inhibition effects to the SW480 cells. In conclusion, our results demonstrated that ORAI1 could mediate TGF-β-Induced EMT by promoting Ca2+ entry and calpain activity in Colorectal Cancer Cells.

scholarly journals LncRNA CRNDE Promoted Colorectal Cancer Cells Reisitance To Paclitaxel Through Wnt/β-Catenin Signaling Pathway

2021 ◽  
Author(s):  
Rui Ma ◽  
Chuan-yang Yu ◽  
Xiang Tao ◽  
Zhi Yang ◽  
Qi Huang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathway ◽  
Colorectal Neoplasia ◽  
Cancer Treatments ◽  
Sw620 Cell ◽  
Invasion And Migration ◽  
Over Expression ◽  
Colorectal Cancer Cells ◽  
Sw620 Cells ◽  
And Migration

Abstract Background The lncRNA colorectal neoplasia differentially expressed (lncRNA CRNDE) is commonly over-expressed in different human cancers and involved in different biological functions. Paclitaxel(PTX) is a tricyclic diterpenoid compound which often used as a natural anticancer drugs in cancer treatments. Although there have many research reports about the mechanisms of LncRNA involved in PTX treatment, there are no any research about lncRNA CRNDE and PTX resistance in colorectal cancer. The purpose of this study is to investigate the mechanisims of LncRNA CRNDE involving PTX resistance in colorectal cancer. Results We constructed lncRNA CRNDE over-expression vector and transfected it into SW620 cell. CCK8, Transwell experiments proved that over-expression of lnc CRNDE increased SW620 cells proliferation and invasion, while the si-CRNDE group was significantly decreased. over-expression CRNDE can significantly up-regulate β-catenin, c-myc, APC and Axin2 expression and affect the expression of cyclinD1 and CDK4 after treated with PTX. Conclusion lncRNA CRNDE promotes CRCs proliferation, invasion and migration. Over-expression of LncRNA CRNDE enhanced the reisitance of CRC to PTX through inhibition of Wnt/ β-catenin signaling pathway.

CircABCC4 Regulates the Proliferation, Migration, and Invasion of Colorectal Cancer SW620 Cells by Targeting Micro RNA-216a-3p

2021 ◽  
Vol 11 (3) ◽  
pp. 548-552
Author(s):  
Yiqian Li ◽  
Haofeng Yuan ◽  
Yibin Chen ◽  
Baoqi Xu ◽  
Yanhong Zhang
Keyword(s):  
Colorectal Cancer ◽  
Micro Rna ◽  
Luciferase Reporter ◽  
Migration And Invasion ◽  
Human Colorectal Cancer ◽  
Cell Behaviors ◽  
Colorectal Cancer Cells ◽  
Sw620 Cells ◽  
Cancer Tissues ◽  
Dual Luciferase Reporter Assay

This work investigates the effect of circABCC4 on the proliferation, migration, and invasion of colorectal cancer SW620 cells; circABCC4’s regulation of miR-216a-3p is also studied. qRT-PCR was used to measure the levels of circABCC4 and miR-216a-3p in colorectal cancer and adjacent tissues. The human colorectal cancer SW620 cells were transfected with different constructs of circABCC4 or miR-216a-3p or both to study their interactions and combined effects on cell behavior. A dual-luciferase reporter experiment tested the targeted relationship between circABCC4 to miR-216a-3p. Furthermore, the behaviors of SW620 cells, such as cell viability, migration, and invasion, were investigated. Also, the proteins related to cell behaviors were investigated with western blotting. Our results showed that colorectal cancer tissues had a higher level of circABCC4 but a lower level miR-216a-3p. The increased level of circABCC4 and the reduced level of miR-216a-3p had analogous influences on the behaviors of SW620 cells, resulting in reduced cell proliferation, migration, and invasion; the levels of related protein were also decreased. Moreover, we found that disrupting miR-548c-3p could reverse the influence of inhibiting circABCC4 on SW620 cells. In addition, the dual-luciferase reporter assay results confirmed the targeting of miR-216a-3p by circABCC4. These data demonstrate that the silencing of circABCC4 may inhibit the proliferation, migration, and invasion of colorectal cancer cells by upregulating miR-548c-3p.

scholarly journals CircHMGCS1 is upregulated in colorectal cancer and promotes proliferation of colorectal cancer cells by targeting microRNA-503-5p

2019 ◽  
Vol 17 ◽  
pp. 205873921986955 ◽  
Author(s):  
Jingqing Dong ◽  
Jun Li ◽  
Jihui Luo ◽  
Weiqiang Wu
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Quantitative Polymerase Chain Reaction ◽  
Clinical Parameter ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Apoptosis Pathway ◽  
Colorectal Cancer Cells ◽  
And Migration ◽  
Related Proteins

This study aims to explore the regulatory mechanism of circHMGCS1/microRNA-503-5p (miR-503-5p) axis during colorectal cancer (CRC) development and progression. Real-time quantitative polymerase chain reaction (RT-qPCR) was applied to evaluate the expression of circHMGCS1 and miR-503-5p in CRC samples and their adjacent non-tumor specimen. Then, cell proliferation and cell apoptosis and migration and invasion of circHMGCS1-knocked down cells were further detected, using cell counting kit-8 (CCK-8), flow cytometry, Transwell assay, and western blotting assays. CircHMGCS1 was found to be significantly upregulated in CRC, and its high expression was closely correlated with the poor clinical parameter. In addition, the knockdown of circHMGCS1 could significantly inhibit CRC cells’ growth promoting apoptosis, as suggested by the expression of apoptosis pathway-related proteins, which changed consistently. Furthermore, miR-503-5p inhibitors were able to reverse the suppression of cell proliferation induced by silencing circHMGCS1. Therefore, circHMGCS1 might serve as a promising bio-marker and treatment target for CRC.

scholarly journals Effects of PKM2 Gene Silencing on the Proliferation and Apoptosis of Colorectal Cancer LS-147T and SW620 Cells

2017 ◽  
Vol 42 (5) ◽  
pp. 1769-1778 ◽  
Author(s):  
Ran Ao ◽  
Lin Guan ◽  
Ying Wang ◽  
Jia-Ni Wang
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Protein Expression ◽  
Gene Silencing ◽  
Cell Counting ◽  
Qrt Pcr ◽  
Empty Plasmid ◽  
Proliferation And Apoptosis ◽  
Mrna And Protein Expression ◽  
Sw620 Cells

Background/Aims: This paper aims to explore the effects of pyruvate kinase (PK) M2 gene silencing on the proliferation and apoptosis of colorectal cancer (CRC) LS-147T and SW620 cells. Methods: CRC LS-147T and SW620 cells highly expressing PKM2 were randomly selected by quantitative real-time polymerase chain reaction (qRT-PCR) and then assigned into the blank (no transfection), PKM2-shRNA (transfection with shRNA) and empty plasmid (transfection with empty plasmid) groups. Immunofluorescence was applied to detect PKM2 protein expression. qRT-PCR and Western blotting were conducted to assess mRNA and protein expression of PKM2, p53 and p21. The cell counting kit-8 (CCK-8) assay was used to assess cell proliferation. Flow cytometry was used to assess the cell cycle and apoptosis rate, and a senescence-associated β-galactosidase staining kit was used to assess cell senescence. Results: PKM2 exhibited high mRNA expression among CRC LS-147T and SW620 cells with remarkable protein expression noted in the cytoplasm and nucleus. The PKM2-shRNA group exhibited reduced PKM2 mRNA and protein expression, whereas p53 and p21 expression was increased compared with the blank and empty plasmid groups. Cell proliferation in PKM2-shRNA cells decreased significantly compared with the blank group and empty plasmid groups. The PKM2-shRNA group exhibited more cells in the G1 phase and fewer cells in the G2/M phase compared with the blank and empty plasmid groups. In addition, the PKM2-shRNA group exhibited significantly increased apoptosis rates and β-galactosidase activity compared with the blank and empty plasmid groups. Conclusion: Our study demonstrates that PKM2 gene silencing suppresses proliferation and promotes apoptosis in LS-147T and SW620 cells.

Butyrate-Induced Apoptosis in HCT116 Colorectal Cancer Cells Includes Induction of a Cell Stress Response

2011 ◽  
Vol 10 (4) ◽  
pp. 1860-1869 ◽  
Author(s):  
Kim Y. C. Fung ◽  
Gemma V. Brierley ◽  
Steve Henderson ◽  
Peter Hoffmann ◽  
Shaun R. McColl ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stress Response ◽  
Cancer Cells ◽  
Cell Stress ◽  
Colorectal Cancer Cells ◽  
A Cell ◽  
Induced Apoptosis ◽  
Cell Stress Response

scholarly journals TCN1 Deficiency Inhibits The Malignancy of Colorectal Cancer Cells By Regulating The ITGB4 Pathway

2021 ◽  
Author(s):  
Xinqiang Zhu ◽  
Xuetong Jiang ◽  
Qinglin Zhang ◽  
Hailong Huang ◽  
Xiaohong Shi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Molecular Mechanisms ◽  
Function Analysis ◽  
Hct116 Cell ◽  
Tumor Xenograft ◽  
Integrin Subunit ◽  
Filamin A ◽  
Loss Of Function ◽  
Colorectal Cancer Cells

Abstract Background: This study aimed to investigate the biological function and regulatory mechanism of TCN1 in colorectal cancer (CRC). Methods: We studied the biological functions of TCN1 using gain-of-function and loss-of-function analysis in HCT116 cell lines, and examined the effects of TCN1 on the proliferation, apoptosis, and invasion of CRC cells and determined its potential molecular mechanisms using CRC lines and mouse xenotransplantation models. Tumor xenograft and tumor metastasis studies were performed to detect the tumorigenicity and metastasis of cells in vivo. Results: TCN1-knockdown attenuated CRC cell proliferation, invasion and promoted cell apoptosis. Overexpression of TCN1 yielded the opposite effects. In addition, TCN1-knockdown HCT116 cells failed to form metastatic foci in the peritoneum after intravenous injection. Molecular mechanism studies showed that TCN1 interacts with integrin subunit β4 (ITGB4) to positively regulate the expression of ITGB4. TCN1-knockdown promoted the degradation of ITGB4 and increased the instability of ITGB4 and filamin A (FLNA). Downregulation of ITGB4 at the protein level resulted in the disassociation of the ITGB4/PLEC complex, leading to cytoskeletal damage. Conclusion: TCN1 might exert oncogenic role in CRC via regulating the ITGB4 signaling pathway.

scholarly journals Anlotinib overcomes multiple drug resistant of the colorectal cancer cells via inactivating PI3K/AKT pathway

2019 ◽  
Author(s):  
Weilan Lan ◽  
Jinyan Zhao ◽  
Haixia Shang ◽  
Jun Peng ◽  
Wujin Chen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Cycle ◽  
Caspase 3 ◽  
Resistance Index ◽  
Akt Pathway ◽  
Multiple Drug ◽  
Drug Resistant ◽  
Multiple Drug Resistant ◽  
Colorectal Cancer Cells ◽  
Induced Apoptosis

AbstractBackgroundAnlotinib is a multi-tyrosine kinase inhibitor that has been reported to have activity against colorectal cancer. However, the functional mechanisms whereby anlotinib mediates against deadly drug-resistant colorectal cancer (CRC) has not been fully described-specifically, the potential mechanisms that inhibit proliferation and induce apoptosis remain largely unknown.MethodsMTT assays were used to detect cell viability and calculate the resistance index. Colony formation was used to evaluate the proliferation of resistant cells. DAPI staining was used to detect cell apoptosis morphologically. Annexin V-FITC with PI staining was used to detect early and late-stage apoptosis of cells. Cell cycle distribution was determined by Flow cytometry. Transwell assays were performed to examine the ability of migration and invasion. Cyclin D1 Survivin, CDK4, Bcl-2, Bax and changes of PI3K/AKT pathway were detected by Western blotting. Compared as a single agent or combined with anlotinib or LY294002, PI3K inhibitor (LY294002) was used to verify whether it inhibited drug-resistant CRC cells by lowering PI3K/AKT.ResultsHCT-8/5-FU cells showed multiple drug resistance. Drug resistance index of 5-FU, ADM and DDP were 390.27, 2.55 and 4.57, respectively. Anlotinib was shown to inhibit cell viability on HCT-8/5-FU and HCT-8 cells for 24 h and 48 h in a dosage- and time-dependent pattern. Compared with 48 h, intervened with anlotinib (0 μM, 10 μM, 20 μM and 40 μM) for 24 h, the HCT-8/5-FU cells were sensitive to anlotinib, and their sensitivity was greater than that of the parent cell line (HCT-8) at 24 h. Further, anlotinib inhibited the number of cloned cells significantly and had a significant inhibitory effect on cell cycle, mainly by blocking G1 transferring to S phase. Moreover, anlotinib could down-regulate the expression of survivin, cyclin D1, CDK4, caspase-3, Bcl-2, MMP-2, vimentin, MMP-9, and N-cadherin, while up-regulating cleaved-caspase-3, Bax and E-cadherin. Anlotinib inhibited the activity of the PI3K/AKT pathway and induced apoptosis in HCT-8/5-FU cells. Using LY294002, a specific PI3K inhibitor, our experiment found anlotinib can inhibit drug-resistant CRC cells by reducing PI3K and p-AKT activity-induce apoptosis.ConclusionsAnlotinib inhibited the proliferation, metastasis and induced apoptosis of HCT-8 / 5-FU cells; and the mechanism could be that anlotinib overcomes multiple drug resistant of the colorectal cancer cells via inactivating PI3K/AKT pathway.

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