scholarly journals Radiosensitization of HER2-positive esophageal cancer cells by pyrotinib

2020 ◽  
Vol 40 (2) ◽  
Author(s):  
Xiangyao Lian ◽  
Cuimin Zhu ◽  
Haishan Lin ◽  
Zhengxing Gao ◽  
Guangxin Li ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Esophageal Cancer ◽  
Dna Repair ◽  
Cancer Cells ◽  
Cell Lines ◽  
Radiation Resistance ◽  
G1 Arrest ◽  
Her2 Positive ◽  
Proliferative Effect ◽  
Esophageal Cancer Cells

Abstract Radiation therapy is a widely used treatment for esophageal cancer. However, radiation resistance might result in a poor prognosis. Overexpression of HER2 has been related to adaptive radiation resistance. Pyrotinib is a HER2 inhibitor that shows an anti-tumor effect in breast cancer. The present study aims to explore the influence of pyrotinib combined with radiotherapy on HER2-positive esophageal cancer cells and explore the underlying mechanism. We screened two cell lines (TE-1 and KYSE30) that highly express HER2 from several human esophageal cancer cell lines. Cells were treated with pyrotinib or/and radiation. Cell proliferation, cell cycle distribution, and cell migration were measured. The protein levels involved in cell cycle and DNA repair were measured by Western blot. Results showed that pyrotinib inhibited HER2 activation and exerted an anti-proliferative effect in TE-1 and KYSE30 cells. Furthermore, it enhanced the anti-proliferative effect of radiation in these two cell lines. These effects might be via inhibiting HER2 phosphorylation, inducing G0/G1 arrest, and reducing EMT and DNA repair. Our results indicated that pyrotinib sensitivitied HER2 positive esophageal cancer cells to radiation treatment through various mechanisms. These findings may provide a new therapeutic strategy for treating HER2 positive esophageal cancer.

scholarly journals Therapeutic and Radiosensitizing Effects of Armillaridin on Human Esophageal Cancer Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Chih-Wen Chi ◽  
Chien-Chih Chen ◽  
Yu-Jen Chen
Keyword(s):  
Cell Cycle ◽  
Esophageal Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Transmembrane Potential ◽  
Mitochondrial Transmembrane Potential ◽  
Cell Counts ◽  
Human Esophageal Cancer ◽  
Esophageal Cancer Cells

Background. Armillaridin (AM) is isolated fromArmillaria mellea. We examined the anticancer activity and radiosensitizing effect on human esophageal cancer cells.Methods. Human squamous cell carcinoma (CE81T/VGH and TE-2) and adenocarcinoma (BE-3 and SKGT-4) cell lines were cultured. The MTT assay was used for cell viability. The cell cycle was analyzed using propidium iodide staining. Mitochondrial transmembrane potential was measured by DiOC6(3) staining. The colony formation assay was performed for estimation of the radiation surviving fraction. Human CE81T/VGH xenografts were established for evaluation of therapeutic activityin vivo.Results. AM inhibited the viability of four human esophageal cancer cell lines with an estimated concentration of 50% inhibition (IC50) which was 3.4–6.9 μM. AM induced a hypoploid cell population and morphological alterations typical of apoptosis in cells. This apoptosis induction was accompanied by a reduction of mitochondrial transmembrane potential. AM accumulated cell cycle at G2/M phase and enhanced the radiosensitivity in CE81T/VGH cells.In vivo, AM inhibited the growth of CE81T/VGH xenografts without significant impact on body weight and white blood cell counts.Conclusion. Armillaridin could inhibit growth and enhance radiosensitivity of human esophageal cancer cells. There might be potential to integrate AM with radiotherapy for esophageal cancer treatment.

PS02.206: THE SYNERGISTIC ANTITUMOR EFFECT OF APATINIB COMBINED WITH CYTOTOXIC DRUGS ON ESOPHAGEAL CANCER

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 180-181
Author(s):  
Feng Wang ◽  
Yanyan Chi ◽  
Xiangrui Meng ◽  
Qingxia Fan
Keyword(s):  
Cell Cycle ◽  
Esophageal Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cytotoxic Drug ◽  
Cytotoxic Drugs ◽  
Migration And Invasion ◽  
Antitumor Effects ◽  
Mrna And Protein Expression ◽  
Esophageal Cancer Cells

Abstract Background Esophageal cancer is one of the most common malignancies in the digestive system in the world. It is difficult to acquire satisfactory effect through chemotherapy which is an essential method to advanced esophageal cancer. Apatinib, a highly selective inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), inhibits the angiogenesis of tumors. Methods The mRNA and protein expression of VEGFR-2 in esophageal cancer cell lines (Eca9706, Eca109, KYSE450, KYSE70) were detected by qRT-PCR and western blot assay. These cell lines were treated with apatinib combined with cytotoxic drugs: cisplatin, paclitaxel, or 5-Fu respectively. Cell proliferation was then measured using CCK-8; cell cycle distribution and apoptosis were analyzed by flow cytometry; cell migration and invasion were evaluated by wound healing and transwell assays. Esophageal cancer xenografts model was established and used to evaluate the the antitumor effects of combination of apatinib and cytotoxic drugs in vivo. Results The mRNA and protein expression of VEGFR-2 were higher in Eca109 and Eca9706 cell lines than those in KYSE70 and KYSE450. The proliferation, migration, and invasion ability of esophageal cancer cells treated with apatinib combined with cytotoxic drugs were lower than those untreated cells. Furthermore, the inhibition effects of apatinib with each cytotoxic drug on the proliferation, migration, and invasion of esophageal cancer cells were greater compared with those treated with either apatinib or cytotoxic drug (P < 0.05). The proportion of G0/G1 phase was increased and the effect of arresting cell cycle were enhanced in esophageal cancer cells treated with apatinib and cytotoxic drugs compared with those treated with either apatinib or cytotoxic drug (P < 0.05). The combination of apatinib with each cytotoxic drug demonstrate synergistic promotion effects on the apoptosis of esophageal cancer cells compared with those treated with either apatinib or cytotoxic drug (P < 0.05). The combination of apatinib with each cytotoxic drug displayed synergistic inhibition effects on the growth of esophageal cancer xenografts compared with those treated with either apatinib or cytotoxic drug (P < 0.05). Conclusion The combination of apatinib with cytotoxic drugs had the synergistic antitumor effects on esophageal cancer. Disclosure All authors have declared no conflicts of interest.

Epigenetic modulation combined with PD-1/PD-L1 blockade enhances immunotherapy based on MAGE-A11 antigen-specific CD8+T cells against esophageal carcinoma

2020 ◽  
Vol 41 (7) ◽  
pp. 894-903
Author(s):  
Yunyan Wu ◽  
Meixiang Sang ◽  
Fei Liu ◽  
Jiandong Zhang ◽  
Weijing Li ◽  
...  
Keyword(s):  
T Cells ◽  
Esophageal Cancer ◽  
Tumor Cell ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cd8 T Cells ◽  
Dna Methyltransferase ◽  
Tumor Cell Lines ◽  
Epigenetic Modulation ◽  
Esophageal Cancer Cells

Abstract Cancer testis antigens (CTAs) are promising targets for T cell-based immunotherapy and studies have shown that certain CT genes are epigenetically depressed in cancer cells through DNA demethylation. Melanoma-associated antigen A11 (MAGE-A11) is a CTA that is frequently expressed in esophageal cancer and is correlated with a poor esophageal cancer prognosis. Consequently, MAGE-A11 is a potential immunotherapy target. In this study, we evaluated MAGE-A11 expression in esophageal cancer cells and found that it was downregulated in several tumor cell lines, which restricted the effect of immunotherapy. Additionally, the specific recognition and lytic potential of cytotoxic T lymphocytes (CTLs) derived from the MAGE-A11 was determined. Specific CTLs could kill esophageal cancer cells expressing MAGE-A11 but rarely lysed MAGE-A11-negative tumor cells. Therefore, induction of MAGE-A11 expression is critical for CTLs recognition and lysis of esophageal cancer cells. Treatment with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine increased MAGE-A11 expression in esophageal cancer cells and subsequently enhanced the cytotoxicity of MAGE-A11-specific CD8+T cells against cancer cell lines. Furthermore, we found that PD-L1 expression in esophageal cancer cells affected the antitumor function of CTLs. programmed death-1 (PD-1)/PD-L1 blockade could increase the specific CTL-induced lysis of HLA-A2+/MAGE-A11+ tumor cell lines treated with 5-aza-2′-deoxycytidine. These findings indicate that the treatment of tumor cells with the DNA methyltransferase inhibitor 5-aza-2′-deoxycytidine augments MAGE-A11 expression in esophageal cancer cells. The combination of epigenetic modulation by 5-aza-2′-deoxycytidine and PD-1/PD-L1 blockade may be useful for T cell-based immunotherapy against esophageal cancer.

scholarly journals Gypenoside L Inhibits Proliferation of Liver and Esophageal Cancer Cells by Inducing Senescence

Molecules ◽  
2019 ◽  
Vol 24 (6) ◽  
pp. 1054 ◽  
Author(s):  
Jingxin Ma ◽  
Xiaopeng Hu ◽  
Chenghui Liao ◽  
Haitao Xiao ◽  
Qinchang Zhu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Esophageal Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Inhibitory Effect ◽  
Cancer Cell Growth ◽  
Therapeutic Drugs ◽  
Cycle Arrest ◽  
Chemical Inhibitors ◽  
Esophageal Cancer Cells

Senescence is an irreversible state of cell cycle arrest that can be triggered by multiple stimuli, such as oxygen reactive species and DNA damage. Growing evidence has proven that senescence is a tumor-suppressive approach in cancer treatment. Therefore, developing novel agents that modulate senescence may be an alternative strategy against cancer. In our study, we investigated the inhibitory effect of gypenoside L (Gyp-L), a saponin isolated from Gynostemma pentaphyllum, on cancer cell growth. We found that Gyp-L increased the SA-β-galactosidase activity, promoted the production of senescence-associated secretory cytokines, and inhibited cell proliferation of human liver and esophageal cancer cells. Moreover, Gyp-L caused cell cycle arrest at S phase, and activated senescence-related cell cycle inhibitor proteins (p21 and p27) and their upstream regulators. In addition, Gyp-L activated p38 and ERK MAPK pathways and NF-κB pathway to induce senescence. Consistently, adding chemical inhibitors efficiently counteracted the Gyp-L-mediated senescence, growth inhibition, and cell cycle arrest in cancer cells. Furthermore, treatment with Gyp-L, enhanced the cytotoxicity of clinic therapeutic drugs, including 5-fluorouracil and cisplatin, on cancer cells. Overall, these results indicate that Gyp-L inhibits proliferation of cancer cells by inducing senescence and renders cancer cells more sensitive to chemotherapy.

scholarly journals Research of the mechanism on miRNA193 in exosomes promotes cisplatin resistance in esophageal cancer cells

2019 ◽  
Author(s):  
Shifeng Shi ◽  
Xin Huang ◽  
Xiao Ma ◽  
Xiaoyan Zhu ◽  
Qinxian Zhang
Keyword(s):  
Cell Cycle ◽  
Drug Resistance ◽  
Esophageal Cancer ◽  
Cancer Cells ◽  
Tumor Cells ◽  
Cisplatin Resistance ◽  
High Expression ◽  
Drug Resistant ◽  
Cellular Resistance ◽  
Esophageal Cancer Cells

AbstractPurposeChemotherapy resistance of esophageal cancer is a key factor affecting the postoperative treatment of esophageal cancer. Among the media that transmit signals between cells, the exosomes secreted by tumor cells mediate information transmission between tumor cells, which can make sensitive cells obtain resistance. Although some cellular exosomes play an important role in tumor’s acquired drug resistance, the related action mechanism is still not explored specifically.MethodsTo elucidate this process, we constructed a cisplatin-resistant esophageal cancer cell line, and proved that exosomes conferring cellular resistance in esophageal cancer can promote cisplatin resistance in sensitive cells. Through high-throughput sequencing analysis of the exosome and of cells after stimulation by exosomes, we determined that the miRNA193 in exosomes conferring cellular resistance played a key role in sensitive cells acquiring resistance to cisplatin. In vitro experiments showed that miRNA193 can regulate the cell cycle of esophageal cancer cells and inhibit apoptosis, so that sensitive cells can acquire resistance to cisplatin. An in vivo experiment proved that miRNA193 can promote tumor proliferation through the exosomes, and provide sensitive cells with slight resistance to cisplatin.ResultsSmall RNA sequencing of exosomes showed that exosomes in drug-resistant cells have 189 up-regulated and 304 down-regulated miRNAs; transcriptome results showed that drug-resistant cells treated with drug-resistant cellular exosomes have 3446 high-expression and 1709 low-expression genes; correlation analysis showed that drug-resistant cellular exosomes mainly affect the drug resistance of sensitive cells through paths such as cytokine–cytokine receptor interaction, and the VEGF and Jak-STAT signaling pathways; miRNA193, one of the high-expression miRNAs in drug-resistant cellular exosomes, can promote drug resistance by removing cisplatin’s inhibition of the cell cycle of sensitive cells.ConclusionSensitive cells can become resistant to cisplatin through acquired drug-resistant cellular exosomes, and miRNA193 can make tumor cells acquire cisplatin resistance by regulating the cell cycle.

Oncolytic adenovirus expressing apoptotic genes targets radiation resistant (RR) esophageal cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21043-21043
Author(s):  
J. Y. Chang ◽  
R. Komaki ◽  
X. Zhang ◽  
L. Wang ◽  
B. Fang
Keyword(s):  
Gene Expression ◽  
Esophageal Cancer ◽  
Radiation Exposure ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Esophageal Cancer Cell ◽  
Esophageal Cancer Cells ◽  
Trans Gene ◽  
Fractionated Radiation

21043 Background: Only 25% of esophageal cancer patients achieve pathological complete response after standard chemoradiotherapy. Radiation dose escalation is associated with higher toxicity but no therapeutic improvement. In addition, esophageal cancer cells may develop radiation resistance (RR) after fractionated radiation exposure. Therefore, molecular targeting therapy for RR esophageal cancer is urgently needed. Methods: Six pairs of RR esophageal cancer cell lines were established by applying continuous 2 Gy fractionated irradiation. Ad/TRAIL-E1, an oncolytic adenoviral vector expressing both apoptotic TRAIL and viral E1A genes under the control of tumor specific human telomerase reverse transcriptase promoter, was constructed. Phosphate buffer solution and vectors expressing the TRAIL gene only, the GFP marker protein only, or the E1A gene only served as controls. Trans-gene expression, apoptosis activation, and the RR esophageal cancer cells targeted were evaluated in vitro and in vivo. A human esophageal RR cancer model was established and locally treated with Ad/TRAIL-E1 or controls. Results: After fractionated radiation exposure, esophageal cancer cell lines developed RR (up to 25-fold) that was associated with activation of the anti-apoptotic pathway. Ad/TRAIL-E1 activated an apoptotic cascade of caspases and selectively killed esophageal cancer cells but not normal cells. Ad/TRAIL-E1 preferentially targeted RR stem-like cancer cells with higher trans-gene expression and cell killing compared with parental cells. Overexpression (3 times) of Coxsackie's and adenoviral receptors in RR esophageal cancer cells compared with parental cells was noted. Ad/TRAIL-E1 therapy resulted in 40% tumor-free survival without the treatment- related toxicity found in human RR esophageal adenocarcinoma mouse models (p<0.05 as compared with controls). Conclusions: Esophageal cancer cells develop RR after fractionated radiation exposure. Ad/TRAIL-E1 preferentially targeted RR stem-like esophageal cancer cells, which resulted in a 40% cure rate. No significant financial relationships to disclose.

Effect of miR-214 on Proliferation, Cell Cycle and Apoptosis of Esophageal Cancer Cells

2021 ◽  
Vol 11 (2) ◽  
pp. 315-319
Author(s):  
Yanfeng Wang ◽  
Hongling Gao ◽  
Hao Wang ◽  
Enguang Lin ◽  
Zhao Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Esophageal Cancer ◽  
Western Blot ◽  
Cancer Cells ◽  
Real Time Pcr ◽  
Cell Number ◽  
G1 Phase ◽  
Specific Mechanism ◽  
Esophageal Cancer Cells

Esophageal cancer seriously affects human health. miR-214 involves in esophageal cancer, but its specific mechanism has not been completely elucidated. Our study investigated miR-214’s role in esophageal cancer. Eca109 cells were transfected with miR-214 inhibitor/NC was transfected into Eca109 cells followed by analysis of miR-214 level by real-time PCR, cell proliferation by CCK8 assay, cell apoptosis and cell cycle and PTEN level by Western blot. miR-214 was significantly upregulated in Eca109 cells (P < 0.01) with downregulated PTEN (P < 0.05). miR-214 inhibitor significantly upregulated PTEN, decreased cell number, increased apoptosis and cells in G1 phase (P < 0.05). PTEN was a target of miR-214. miR-214 affects esophageal cancer cells by targeting PTEN.

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