Purpose To investigate the effects of hypoxia inducible factor-2α (HIF-2ot) siRNA on proliferation and chemotherapy sensitivity of breast carcinoma MCF-7.Methods RNA interference was used to silence the expression of HIF-2α in MCF-7 cells.The changes of HIF-2α gene expression were detected by immunocytochemistry and RT-PCR.Under hypoxia environment simulated by CoCl2,MTT assay and flow cytometry (FCM) were used to measure cell growth inhibition rate and cell apoptosis of MCF-7 cells under different dosages of chemotherapeutic agents (5-fluorouracil,adriamycin,and paclitaxel).Results Expression of HIF-2α in MCF-7 were down-regulated by HIF-2α siRNA (P ＜ 0.05).The proliferation inhibition and apoptosis rates were evidently increased after transfection with HIF-2α siRNA (P ＜ 0.05),chemotherapy drug sensitivity was enhanced.Conclusion HIF-2α siRNA can induce the apoptosis and inhibit the proliferation and enhance the sensitivity of breast carcinoma MCF-7 cell line to chemotherapeutic agents.Blocking HIF-2α maybe a very promising strategy for breast carcinoma gene therapy in combination with chemotherapy.

Purpose To investigate the expression and re-lationship of phosphatidic acid phosphatase 2 domain 1A(PPAPDC1A),also known as phospholipid phosphatase 4(PLPP4),in colorectal cancer(CRC)tissues and different colorectal cancer cells.Methods Immunohistochemical EnVi-sion method was applied to detect the expression of PPAPDC1A in 60 CRC tissues and paired paracancerous tissues.Stable over-expression and silencing cell lines of PPAPDC1A were success-fully constructed by gene transfection,and the effects of this gene on different colorectal cancer cell lines were investigated by CCK-8,Transwell,subcutaneous tumor formation in nude mice and tail vein injection in nude mice.Results PPAPDC1A ex-pression was upregulated in CRC tissues compared with paracan-cerous tissues,and the intensity of PPAPDC1A expression was negatively correlated with cell differentiation(P=0.011).PPAPDC1A stable overexpression and interference cell lines were successfully constructed.The results of in vitro and in vivo experiments showed that the growth rate(SW480-PPAPDC1A,RKO-PPAPDC1A groups:0.38±0.03,0.25±0.01),the number of cells crossing the compartment(SW480-PPAPDC1 A,RKO-PPAPDC1A groups:218.33±7.09,96.33±1.52),the number of clone formation(SW480-PPAPDC1 A,RKO-PPAP-DC1A groups:174.33±5.03,245.00±7.00),the in vivo tumor volume(4.16±0.91),and the number of lung metasta-sis in nude mice(5.1±3.84)were significantly higher in the PPAPDC1A stably overexpressing cell lines compared with the Vector group(P＜0.05).However,the growth rate(SW620-shPPAPDC1A,LOVO-shPPAPDC1A groups:0.14±0.02,0.16±0.05),number of cells crossing the chambers(SW620-shPPAPDC1A,LOVO-shPPAPDC1A groups:13.33±0.57,18.33±0.51),number of clone formation(SW620-shPPAP-DC1A,LOVO-shPPAPDC1A groups:28.33±1.52,8.67± 0.57),tumor volume(0.56±0.21),and number of lung me-tastasis in nude mice(1.2±1.03)were significantly lower(P＜0.05)in the PPAPDC1 A-silenced cell line compared with the NC group.Conclusion Down-regulation of PPAPDC1A expres-sion inhibits the proliferation,invasion,migration and metastatic ability of CRC cells.