The Anti-tumor Effect And Mechanism Of CDK4/6 Inhibitor Palbociclib In Small Cell Lungcancer Cell Lins

Objectives:Small cell lung cancer(SCLC)accounts for 15-20% of lung cancer,the death rate is very high,and the 5-year survival rate is smaller 2%.Most patients are already in the extensive stage when diagnosed,for patients with extensive stage SCLC,chemotherapy are the primary therapy method,but during the treatment,SCLC is generally resistant to chemotherapy drugs,tumor recurrence is inevitable,so the development of new drugs is crucial.In recent years,Targeted therapies are becoming more and more popular in the treatment of patients with non-small cell lung cancer,but they are still in the experimental stage in the treatment of SCLC patients,and there are no targeted drugs that can be applied to patients with SCLC.CDK4/6 inhibitor is a targeted therapy drug and is currently the focus of clinical research.CDK4/6 inhibitors can arrest the cell cycle in the G1 phase,promote cell apoptosis,and achieve anti-tumor effects.Palbociclib is the first CDK4/6inhibitor used in clinical treatment,the drug has been approved by the FDA for use in postmenopausal estrogen receptor positive breast cancer.However,the anti-tumor effect of palbociclib in SCLC patients and its potential mechanism have not been elucidated.Therefore,this study used SCLC cell lines DMS114 and H1688 cells as the research object to explore the effect of palbociclib on the biological behavior of SCLC cells and its potential mechanism.Methods:1.The effects of palbociclib on the apoptosis and proliferation of SCLC cells were investigated by MTT,clone formation experiment and flow cytometry.2.Analyze the expression of CDK4,CDK6,mTOR,and TSC2 in patients with SCLC through GEO database.3.The effects of palbociclib on mTOR and TSC2 mRNA and protein expression levels in SCLC cells were explored by qRT-PCR and western blotting experiments.Results:1.Palbociclib can inhibit the proliferation and promote the apoptosis of SCLC cells.2.Through the analysis of GSE43346 data set in GEO database,it was found that compared with normal people,CDK4 and m TOR were highly expressed in SCLC patients,while CDK6 and TSC2 were lowly expressed.3.Palbociclib can reduce the mRNA and protein expression levels of mTOR,and increase the mRNA and protein expression levels of TSC2.4.Palbociclib exerts an antitumor effect on SCLC cell lines by down-regulating mTOR.Conclusions:In general,palbociclib can promote the apoptosis and inhibited the proliferation of SCLC cells by down-regulating mTOR,and thus achieving the anti-tumor effect.This suggests that palbociclib may be a potential treatment for patients with SCLC.