Effect of siRNA-induced Atg7 gene silencing on the sensitivity of ovarian cancer SKOV3 cells to cisplatin.

Ovarian cancer is one of the most common types of gynecological malignant tumors. A proclivity for, or the development of chemoresistance severely affects treatment efficacy for ovarian cancer. Herein we found that as concentrations of cisplatin (DDP) used in SKOV3 cells increased, expression of intracellular reactive oxygen species (ROS) increased as did amounts of proteins of Beclin-1 and Autophagy-Related Gene 7 (Atg7) whereas in contrast, expression of P62 protein decreased gradually. Expression of Atg7 protein in SKOV3 cells in the siRNA-Atg7 transfection treatment group was significantly reduced compared to the negative control group. Post-application of DDP treatments, the apoptotic ratio of SKOV3 cells in the siRNA-Atg7 transfection group increased, and the cell survival rate decreased to a level significantly lower than in the negative control group. Cellular morphological analyses revealed remarkably decreased measures of cell density, as well as shrunk, deformed, and rounded cells with unclear boundaries, and revealed a decreased measures of mitochondrial membrane potential. Taken together, autophagy may be involved in the dynamics and mechanistics underlying DDP resistance in ovarian cancer SKOV3 cells. Thus, inhibition of autophagy through down-regulation expression of Atg7 may have beneficially enhanced the sensitivity of SKOV3 cells to DDP-based chemotherapy which could help improve treatment outcomes for patients afflicted by ovarian cancer.

[1]  P. Ren,et al.  Autophagy Inhibitor (LY294002) and 5-fluorouracil (5-FU) Combination-Based Nanoliposome for Enhanced Efficacy Against Esophageal Squamous Cell Carcinoma , 2018, Nanoscale Research Letters.

[2]  Wei Zhou,et al.  Inhibiting ROS-TFE3-dependent autophagy enhances the therapeutic response to metformin in breast cancer , 2018, Free radical research.

[3]  Juliana S. C. Monteiro,et al.  ROS-induced autophagy reduces B16F10 melanoma cell proliferative activity , 2018, Lasers in Medical Science.

[4]  Kwok-Kin Wong,et al.  Autophagy Sustains Pancreatic Cancer Growth through Both Cell-Autonomous and Nonautonomous Mechanisms. , 2018, Cancer discovery.

[5]  X. Bian,et al.  Autophagy-induced KDR/VEGFR-2 activation promotes the formation of vasculogenic mimicry by glioma stem cells , 2017, Autophagy.

[6]  Min Jae Lee,et al.  p62/SQSTM1/Sequestosome-1 is an N-recognin of the N-end rule pathway which modulates autophagosome biogenesis , 2017, Nature Communications.

[7]  Haley R. Pugsley,et al.  Assessing Autophagic Flux by Measuring LC3, p62, and LAMP1 Co-localization Using Multispectral Imaging Flow Cytometry , 2017, Journal of visualized experiments : JoVE.

[8]  B. Győrffy,et al.  ADIPOQ/adiponectin induces cytotoxic autophagy in breast cancer cells through STK11/LKB1-mediated activation of the AMPK-ULK1 axis , 2017, Autophagy.

[9]  M. Hermann,et al.  C10ORF10/DEPP-mediated ROS accumulation is a critical modulator of FOXO3-induced autophagy , 2017, Molecular Cancer.

[10]  G. J. Yoshida.  Therapeutic strategies of drug repositioning targeting autophagy to induce cancer cell death: from pathophysiology to treatment , 2017, Journal of Hematology & Oncology.

[11]  Wei Zhang,et al.  MIR506 induces autophagy-related cell death in pancreatic cancer cells by targeting the STAT3 pathway , 2017, Autophagy.

[12]  Xiang Wu,et al.  Benzyl isothiocyanate induces protective autophagy in human lung cancer cells through an endoplasmic reticulum stress-mediated mechanism , 2017, Acta Pharmacologica Sinica.

[13]  M. Liao,et al.  Absence of autophagy promotes apoptosis by modulating the ROS-dependent RLR signaling pathway in classical swine fever virus-infected cells , 2016, Autophagy.

[14]  Shaohui Huang,et al.  Decreased expression of Beclin-1 is significantly associated with a poor prognosis in oral tongue squamous cell carcinoma , 2016, Molecular medicine reports.

[15]  Jia-Lei Sun,et al.  Effects of 5‑fluorouracil and class III phosphoinositide 3‑kinase small interfering RNA combination therapy on SGC7901 human gastric cancer cells. , 2015, Molecular medicine reports.

[16]  N. Mizushima,et al.  Autophagy and human diseases , 2013, Cell Research.

[17]  M. Kool,et al.  Histone deacetylase 10 promotes autophagy-mediated cell survival , 2013, Proceedings of the National Academy of Sciences.

[18]  K. Lim,et al.  Why is autophagy important in human diseases? , 2012, Experimental & Molecular Medicine.

[19]  Robert Brown,et al.  Therapeutic modulation of epigenetic drivers of drug resistance in ovarian cancer , 2010, Therapeutic advances in medical oncology.