CyPA Increase The Sensitivity Of Cancer Cells In Nude Mice To Cisplatin

Purpose:Cyclophilin A(CyPA) is the most important and firstly founded member ofCyclophilins. It was firstly concerned as a cytosolic binding protein of theimmuno-suppressive drug cyclosporin A(CsA). And it is a widely expressed proteinin nature possessing PPIase and chaperone activities which help the precise folding ofprotein. Also, it is involved in immunosuppression, inflammation and the balance ofcholesterol. The study found that CyPA plays multiple roles in increasing cellproliferation, invasion, metastasis and drug resistant in various cancer cell typeswhich is closely related with its PPIase activity. We intend to inhibition the PPIaseactivity and investigate the effects on cell proliferation, cisplatin sensibility in vivo.We hope to discover a new gene therapeutic targets for lung cancer.Methods:We used lentivirus-mediated RNA interference approach in H1299cell line toinhibit CyPA mRNA expression. Real-time PCR and Western-blot was used todetect the CyPA expression level in H1299. Female nude mice were randomly dividedinto3groups, which is H1299wild-type cell line,H1299gene silencing cell line andH1299negative control cell line respectively. Cell inoculation xenograft model andtissue slices inoculation xenograft model were constructed and tumor size and tumorweight was measured.CyPA immunohistochemistry were observed to explore CyPAeffects on cell proliferation. Nude mice were randomly divided into four groups,namely the control group (saline), CIS (cisplatin) monotherapy group, CsA group(PPIase inhibitors), and the Cis with CsA combination therapy group. Tissue slicesinoculation xenograft model were used. The tumor size and tumor weight wereobserved to explore CyPA effects on tumor sensibility to cisplatin.Results:CyPA mRNA expression was supressed in H1299cells after the infection oflentivirus.The model of xenograft was established successfully. the proliferation ofH1299was obviously slowed down by transduced Lv-shCyPA and tumor sensibility to cisplatin was increased by PPIase inhibition compared to the control groups in vivo.Conclusion:CyPA can promote the proliferation of H1299cells in vivo and increase thetolerance of H1299cells to cisplatin, it could become the target of a new genetargeted therapy. Background:Previous studies investigating the association of physical activity with risk of lungcancer reported conflicting results. In order to update and improve available evidenceon the association above, a meta-analysis was performed.Method:We searched the PubMed database for prospective cohort studies investigating theassociation of physical activity with risk of lung cancer. Pooled relative risk (RR)with its95%confidence intervals (95%CI) was used to assess the association betweenphysical activity and risk of lung cancer.Results:We included14prospective studies with a total of1,644,305participants, with14,074incident lung cancer cases documented during follow-up. Meta-analysis oftotal14studies suggested both high and medium level of physical activity wereassociated with decreased risk of lung cancer compared to the reference group withlow level of physical activity (For high level, RR=0.77,95%CI0.73–0.81, P <0.001; For medium level, RR=0.87,95%CI0.83–0.90, P <0.001). Subgroupanalyses by gender found obvious associations above both in men and women. Nopublication bias was observed.Conclusion:Our findings suggest that high and medium level of physical activity have abeneficial effect on lung cancer by reducing the overall risk of incident lung canceramong both men and women.