The Study Of Cell Proliferation And Apoptosis And Autophagy In Renal Cell Carcinoma Cells Influence By The PI3K/AKT/mTor Inhibitor NVP-BEZ235

Renal cell carcinoma (RCC) is the most common form of kidneycancer, accounting for approximately3%of adult malignancies. WithinRCC, clear cell histology is most prevalent, accounting for80–90%ofcases. Despite the lack of RCC screening, most patients present withlocalized RCC and many can be cured with radical nephrectomy.However,20–30%of patients treated with surgery will relapse, despitehaving no evidence of metastases at diagnosis.The hypervascular tumor renal cell carcinoma (RCC) representsapproximately3%of all adult malignancies. Although patients withearly-stage RCC can be cured surgically, most RCC patients developadvanced metastatic disease, which has poor prognosis. Treatments suchas traditional chemotherapy, hormone therapy, radiation therapy orimmunotherapy provide only limited benefit in metastatic RCC patients.Therefore, new therapeutic strategies are urgently needed in themanagement of advanced RCC. The PI3K/Akt/mTOR signalingpathway regulates several normal cellular functions that are also criticalfor tumorigenesis, including cellular proliferation, growth, survival andmotility. Several studies showed that the PI3K/AKT/mTOR pathway isabnormally overexpressed in RCC, making it an attractive target foranticancer therapy. These data also imply that the PI3K/AKT/mTORpathway is involved in RCC development. In addition, mTOR inhibitors led to RCC apoptosis both in vitro and in vivo.In cell biology, autophagy, or autophagocytosis, is a catabolicprocess involving the degradation of a cell’s own components throughthe lysosomal machinery. It is a tightly regulated process that plays apart in normal cell growth, development and homeostasis, helping tomaintain a balance between the synthesis, degradation and recycling ofcellular products. It is a major mechanism by which a starving cellreallocates nutrients from unnecessary processes to more essentialprocesses.NVP-BEZ235, a novel dual inhibitor, showed great antitumorbenefit and provided a treatment strategy in RCC. Apart fromparticipation in cell proliferation, the PI3K/AKT/mTOR pathway alsoinhibits cell autophagy, which would protect cell against apoptosiscaused by chemotherapeutic drugs. Therefore, combined application ofNVP and autophagy inhibitor may enhance NVP-induced apoptosis.Objective：The research is to study the cell proliferation andapoptosis and autophagyin renal cell carcinoma cells influence by thePI3K/AKT/mTor inhibitor NVP-BEZ235. Looking for a new treatmentstrategy of renal cell carcinomaMethods：we test the effect of NVP on survival rate, apoptosis andautophagy in the RCC cell line,786-0. We also explore the hypothesisthat NVP, in combination with autophagy inhibitors, leads to apoptosisenhancement in786-0cells.Results： the PI3K/AKT/mTOR pathway proteins p-AKT andp-P70S6K were highly expressed in RCC tissue. We also showed thatNVP inhibited cell growth and induced apoptosis and autophagy in RCC cells. The combination treatment of NVP with autophagy inhibitorsenhanced the effect of NVP on suppressing786-0growth and inductionof apoptosis.Conclusion: PI3K/AKT/mTOR signaling pathways protein in renalcell carcinoma tissues expression levels; PI3K/mTOR inhibitor NVP-BEZ235can significantly inhibit renal cell786-0cell proliferation andpromote the occurrence of apoptosis; Autophagy inhibitor cansignificantly improve the NVP-BEZ235cause786-0proliferationinhibition and apoptosis.