Study On The Expression And Function Of Pinx1 In Lung Cancer

Backgroud and objective: Lung cancer is the world's leading cause of cancer mortality.In 2009,the mortality rate of lung cancer in China reached 49.6/100,000 in urban population and 3964/100,000 in rural population,ranking first in all malignant tumors.Lung cancer can be divided into non-small cell lung cancer(NSCLC)and small cell lung cancer(SCLC)according to the pathological characteristics.Non small cell lung cancer accounts for 85% of all lung cancer,including,adenocarcinoma,squamous cell carcinoma and large cell carcinoma.The overall 5-year survival rate for non-small cell lung cancer is only 15%-16%.The molecular mechanism of malignant progression of non-small cell lung cancer remains to be studied.PIN2 / TERF1 interacting telomerase inhibitor 1(PinX1)is an intrinsic telomerase inhibitor,which is abnormally expressed in many tumors.However,PinX1 plays different roles in different types of tumors,and its expression and functional significance in lung cancer are not fully understood.Recent studies show that PinX1 is a microtubule binding protein that regulates the segregation of chromosomes during cell division.Paclitaxel is a conventional first-line chemotherapeutic drug acting on microtubules,which can make the dynamic balance between them lose,induce and promote tubulin polymerization,prevent depolymerization and stabilize microtubules.This study explored the expression and functional significance of pinX1 in lung cancer,and explored the role of pinX1 in paclitaxel-induced killing of lung cancer cells Methods: 158 patients were selected,including 57 adenocarcinoma and 101 squamous cell carcinoma;immunohistochemical staining of PinXl protein in the above samples;statistical analysis of PinXl expression in non-small cell lung cancer and its correlation with clinicopathological characteristics and prognosis;A549 and H520 cell cultures in vitro;lentivirus-mediated fine cells The over-expression of PinXl was detected by MTT,Transwell migration and scratch test,and the proliferation,invasion and migration of PinXl-overexpressed cells were compared with those of normal cell lines,and telomerase activity was detected by telomeric repeat amplification protocol.MTS kit was used to detect the inhibitory effect of paclitaxel or docetaxel on the growth of PinXl overexpressed lung cancer cells.Western blotting was used to detect the expression of Caspase-3,an apoptosis indicator,in the two cells before and after paclitaxel or docetaxel treatment.Results: PinXl protein expression was detected successfully in 158 patients,41 were positive and 117 were negative,the positive rate was 25.95%.Correlation analysis showed that PinXl expression was associated with gender,smoking history,histological subtype,T stage,N stage,recurrence and metastasis.Survival analysis revealed that PinXl expression was correlated with prognosis,and the higher PinXl expression,the better prognosis.The over-expression or down-regulation of PinXl protein in two cell lines was successfully mediated and helped by lentivirus.Otocol assay showed that PinXl overexpressed cells showed low telomerase activity;CCK-8 assay,Transwell migration assay and scratch assay showed that PinXl overexpressed cells resulted in decreased cell proliferation,infection and mobility;down-regulation of PinX1 increased the expression of taxol and docetaxel in H520 and A549 cells The caspase-3 expression was significantly decreased after treatment with paclitaxel or docetaxel,and the micronucleus formation induced by paclitaxel and docetaxel was increased after down-regulation of PinX1.Conclusion: PinXl expression has a certain correlation with prognosis,the higher PinXl expression,the better prognosis;PinXl protein reduces the proliferation and migration of lung cancer cells by reducing telomerase activity.Down regulation of PinX1 enhanced the sensitivity of lung cancer cells to paclitaxel drugs.PinX1 is a multifunctional protein,which plays different roles in different biological processes and has complex regulation in cells.This study provides some evidence for PinXl as a tumor suppressor marker of NSCLC,and provides a theoretical basis for further understanding the role of PinXl in taxol chemotherapeutic agents killing NSCLC cells.