Inhibition of mTOR enhances radiosensitivity of lung cancer cells and protects normal lung cells against radiation

2016 ◽  
Vol 94 (3) ◽  
pp. 213-220 ◽  
Author(s):  
Hang Zheng ◽  
Miao Wang ◽  
Jing Wu ◽  
Zhi-Ming Wang ◽  
Hai-Jun Nan ◽  
...  

Radiotherapy has been used for a long time as a standard therapy for cancer; however, there have been no recent research breakthroughs. Radioresistance and various side-effects lead to the unexpected outcomes of radiation therapy. Specific and accurate targeting as well as reduction of radioresistance have been major challenges for irradiation therapy. Recent studies have shown that rapamycin shows promise for inhibiting tumorigenesis by suppressing mammalian target of rapamycin (mTOR). We found that the combination of rapamycin with irradiation significantly diminished cell viability and colony formation, and increased cell apoptosis, as compared with irradiation alone in lung cancer cell line A549, suggesting that rapamycin can enhance the effectiveness of radiation therapy by sensitizing cancer cells to irradiation. Importantly, we observed that the adverse effects of irradiation on a healthy lung cell line (WI-38) were also offset. No enhanced protein expression of mTOR signaling was observed in WI-38 cells, which is normally elevated in lung cancer cells. Moreover, DNA damage was significantly less with the combination therapy than with irradiation therapy alone. Our data suggest that the incorporation of rapamycin during radiation therapy could be a potent way to improve the sensitivity and effectiveness of radiation therapy as well as to protect normal cells from being damaged by irradiation.

2020 ◽  
Vol 10 (3) ◽  
pp. 109 ◽  
Author(s):  
Hee Sung Chae ◽  
Minchan Gil ◽  
Subbroto Kumar Saha ◽  
Hee Jeung Kwak ◽  
Hwan-Woo Park ◽  
...  

Lung cancer remains the most dangerous type of cancer despite recent progress in therapeutic modalities. Development of prognostic markers and therapeutic targets is necessary to enhance lung cancer patient survival. Sestrin family genes (Sestrin1, Sestrin2, and Sestrin3) are involved in protecting cells from stress. In particular, Sestrin2, which mainly protects cells from oxidative stress and acts as a leucine sensor protein in mammalian target of rapamycin (mTOR) signaling, is thought to affect various cancers in different ways. To investigate the role of Sestrin2 expression in lung cancer cells, we knocked down Sestrin2 in A549, a non-small cell lung cancer cell line; this resulted in reduced cell proliferation, migration, sphere formation, and drug resistance, suggesting that Sestrin2 is closely related to lung cancer progression. We analyzed Sestrin2 expression in human tissue using various bioinformatic databases and confirmed higher expression of Sestrin2 in lung cancer cells than in normal lung cells using Oncomine and the Human Protein Atlas. Moreover, analyses using Prognoscan and KMplotter showed that Sestrin2 expression is negatively correlated with the survival of lung cancer patients in multiple datasets. Co-expressed gene analysis revealed Sestrin2-regulated genes and possible associated pathways. Overall, these data suggest that Sestrin2 expression has prognostic value and that it is a possible therapeutic target in lung cancer.


2018 ◽  
Vol 6 (2) ◽  
pp. 48-53 ◽  
Author(s):  
Wang Zhen-fei ◽  
Liu Li ◽  
Liang Lin ◽  
Hao Qin

Abstract Objective The aim of this study was to investigate the effect of Radix Glehniae on the migration and invasion abilities of lung cancer cells. Methods Normal bronchial cell line 16HBE and lung cancer cell line SK-MES-1 were treated with Radix Glehniae extract. Proliferation, migration, and invasion abilities were determined by Cell Counting Kit (CCK)-8, Transwell, and Matrigel assays, respectively. The expression and secretion levels of tissue inhibitor of metalloproteinases 2 were detected by quantitative PCR and enzyme-linked immunosorbent assay, respectively. Results Radix Glehniae extract inhibited the migration and invasion abilities of SK-MES-1 cells and enhanced TIMP2 expression and secretion by SK-MES-1 cells, without causing toxicity to 16HBE cells. Conclusion Radix Glehniae is useful in lung cancer treatment.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Lérida Liss Flores Villavicencio ◽  
Gustavo Cruz-Jiménez ◽  
Gloria Barbosa-Sabanero ◽  
Carlos Kornhauser-Araujo ◽  
M. Eugenia Mendoza-Garrido ◽  
...  

The effects of organic and inorganic forms of selenium (Se) on human cells have been extensively studied for nutritional concentrations; however, to date, little is known about the potential toxicity at supranutritional levels. In the present study we determined the effects of sodium selenite (SSe) and selenomethionine (SeMet) on cell growth and intracellular structures in lung cancer cells exposed at Se concentrations between 0 and 3 mM. Our results showed that SSe affected cell growth more rapidly than SeMet (24 h and 48 h, resp.). After 24 h of cells exposure to 0.5, 1.5, and 3 mM SSe, cell growth was reduced by 10, 50, and 60%, as compared to controls. After 48 h, nuclear fragmentation was evident in cells exposed to SSe, suggesting an induction to cell death. In contrast, SeMet did not affect cell proliferation, and the cells were phenotypically similar to controls. Microtubules and microfilaments structures were also affected by both Se compounds, again SSe being more toxic than SeMet. To our knowledge, this is the first report on the differential effects of organic and inorganic Se in supranutritional levels in lung cancer cells.


Nanomedicine ◽  
2019 ◽  
Vol 14 (17) ◽  
pp. 2355-2371 ◽  
Author(s):  
Shivani Thoidingjam ◽  
Ashu Bhan Tiku

Aim: Present work was undertaken to fabricate iron oxide nanoparticles (IONPs) using a green approach for increased therapeutic efficacy. Materials & methods: Two types of IONPs were synthesized, one without any coating (IONPUC) and other coated with Phyllanthus emblica (Amla) fruit extract (IONPA). Both the IONPs were characterized using different techniques and therapeutic efficacy was evaluated in A549 human lung cancer cell line. Results: IONPA were smaller in size with better dispersibility compared with IONPUC. They induced increased reactive oxygen species production, higher DNA damage and apoptosis, which resulted in increased toxicity to cancer cells in comparison to IONPUC. Conclusion: Higher uptake of IONPA and active components coating the surface, may be responsible for the increased therapeutic efficacy in cancer cells.


2021 ◽  
Vol 15 (5) ◽  
pp. 1282-1284
Author(s):  
Moein Shaneh

Chemotherapy is a type of cancer treatment in which the lack of selective cytotoxicity often leads to intolerable side effects. Today, the use of medicinal plants is essential in treating cancer due to their fewer side effects. Lagenaria siceraria Standl is critical for cytotoxicity studies due to its polyphenolic, cucurbitacins, pectin, flavonoids, and saponin compounds. In this study, the cytotoxic effects of plant fruit extract were investigated on lung cancer cell lines. To this end, the hydroalcoholic extract of the plant fruit was initially prepared by the percolation method. Then, the effects of solutions containing samples with different concentrations (5000, 500, 1000, 100, 100, 250, 10, 1, 0.1μg.ml-1) were investigated by MTT assay on lung cancer cell line (A549). Cisplatin was considered as a positive control. Statistical calculations were carried out using Prism V.3 software to compare IC50, and the data were analyzed by analysis of variance (ANOVA) and t-test. The results indicated that the IC50 level of cisplatin anti-cancer drug, as a common drug in the market, is significantly lower than Lagenaria siceraria extract. However, the extract of this plant revealed a significant growth inhibitory effect on lung cancer cells. The results also showed that Lagenaria siceraria extract is an effective cytotoxic compound on lung cancer cells. More extensive studies are needed to find effective plant extracts compounds to find and design new and effective cancer treatment drugs. Keywords: Lagenaria siceraria, Cell line, Lung cancer, IC50, MTTassay


2010 ◽  
Vol 38 (02) ◽  
pp. 401-413 ◽  
Author(s):  
Meng Xu ◽  
Liang-He Sheng ◽  
Xi-Hai Zhu ◽  
Shi-Bin Zeng ◽  
Guo-Jun Zhang

This research is aimed on reversing multidrug resistance (MDR) of chemotherapy in lung cancer. According to our previous research, chemotherapeutic drugs resistance in lung cancer is mainly due to high expression of multidrug resistance-associated protein (MRP) gene and activation of caspases. The effect of stephania tetrandra-containing Chinese herbal formula, namely Supplement Energy and Nourish Lung (SENL), is effective in enhancing efficacy and reducing toxicity of chemotherapy in lung cancer. However, the underlying mechnism is largely unknown. To understand whether and how SENL herbs function on multidrug-resistance lung cancer cells, we treated a multidrug resistance lung cancer cell line, SW1573/2R120 with SENL herbs alone or together with a chemotherapeutic drug, Adriamycin (ADM). We observed that SENL herbs had a significant synergistic effect with ADM in inhibiting the growth of SW1573/2R120 cells. SENL alone and particularly together with ADM could significantly increase cell apoptotic death via mitochondria- and caspase-dependent pathway. Furthermore, we showed that SENL herbs could reverse drug resistance of lung cancer cells by decreasing MRP expression and increasing accumulation of intracellular ADM, which in turn increase the sensitivity of cancer cells to ADM. Taken together, the mechanism underlying reversal effect of drug resistance by SENL treatment was reported here and further systematical investigation on SENL herbs may lead to solve drug resistance in lung cancer chemotherapy.


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e19095-e19095
Author(s):  
Z. Gao ◽  
B. Han ◽  
J. Teng

e19095 Backgrounds: Recent studies reported that zoledronic acid, a biphosphonate with proposed apoptotic activity, could cause a direct antitumor effect. Our prior study [J Clin Oncol 26: 2008 (May 20 suppl; abstr 19116)] reported that Zoledronic acid combined with Cisplatin shows significantly synergistic antitumor effects on lung cancer cell line A549 and subcutaneous implanted tumor on nude mice. Investigate whether zoledronic acid, augmented the cytotoxicity of cisplatin and/or paclitaxel in A549 lung cancer cell line. Methods: This cell line was subjected to different concentrations of the above chemotherapeutic agents and zoledronic acid. Cytotoxicity was assessed by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide) assay. Flow cytometry was used to examine cell cycle,cell apoptosis rate. Results: Zoledronic acid in in 50 micromolar (mM) concentration augmented the cytotoxicity by cisplatin in 10μmol/L and paclitaxel in 5μmol/L. Zoledronic acid could inhibit the proliferation of lung cancer cells in vitro,which was associated with arresting of G1 phase and inducing apoptosis by a time-dependent and dose-dependentmanner. The apoptosis rate of cell increased after zoledronic acid combined with cisplatin and/or paclitaxel. Conclusions: Zoledronic acid can induce apoptosis and block cell cycle of lung cancer cells. Zoledronic acid has also shown synergistic antitumor effects when combined with cisplatin and/or paclitaxel. The clinical potential of this finding should be further studied. No significant financial relationships to disclose.


PLoS ONE ◽  
2019 ◽  
Vol 14 (7) ◽  
pp. e0219597 ◽  
Author(s):  
Rosa Camerlingo ◽  
Roberta Miceli ◽  
Laura Marra ◽  
Giuseppina Rea ◽  
Igea D’Agnano ◽  
...  

Micromachines ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1147
Author(s):  
Yugyung Jung ◽  
Minkook Son ◽  
Yu Ri Nam ◽  
Jongchan Choi ◽  
James R. Heath ◽  
...  

Cancer is a dynamic disease involving constant changes. With these changes, cancer cells become heterogeneous, resulting in varying sensitivity to chemotherapy. The heterogeneity of cancer cells plays a key role in chemotherapy resistance and cancer recurrence. Therefore, for effective treatment, cancer cells need to be analyzed at the single-cell level by monitoring various proteins and investigating their heterogeneity. We propose a microfluidic chip for a single-cell proteomics assay that is capable of analyzing complex cellular signaling systems to reveal the heterogeneity of cancer cells. The single-cell assay chip comprises (i) microchambers (n = 1376) for manipulating single cancer cells, (ii) micropumps for rapid single-cell lysis, and (iii) barcode immunosensors for detecting nine different secretory and intracellular proteins to reveal the correlation among cancer-related proteins. Using this chip, the single-cell proteomics of a lung cancer cell line, which may be easily masked in bulk analysis, were evaluated. By comparing changes in the level of protein secretion and heterogeneity in response to combinations of four anti-cancer drugs, this study suggests a new method for selecting the best combination of anti-cancer drugs. Subsequent preclinical and clinical trials should enable this platform to become applicable for patient-customized therapies.


2014 ◽  
Vol 926-930 ◽  
pp. 1061-1064
Author(s):  
Yan Li Xi ◽  
Xiang Qun Wu ◽  
Jie Yu ◽  
Wei Guo Xu ◽  
Tong Zhao ◽  
...  

It is a good therapeutic method that add exogenous ROS to trigger oxidative stress causing death of cancer cells. In the present study, we investigated the inhibitory effects of 3,4,5-trihydroxybenzoic acid (TBA), a polyhydroxyphenolic compound, on high metastatic human lung cancer cell line (95-D) based on inducing reactive oxygen species (ROS). The experiments in vitro showed that 95-D cell viability was inhibited by various amounts of TBA and death was induced in a dose-dependent manner. The possible mechanism was that TBA can induce cell death by decreasing mitochondrial membrane potential (MMP; ΔΨm) and increasing hydrogen peroxide (H2O2) level. These results imply that TBA efficiently induces death in 95-D lung cancer cells and that TBA exerts cytotoxicity on cancer cells by its pro-oxidative activity.


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