Down-regulation of phospho-non-receptor Src tyrosine kinases contributes to growth inhibition of cervical cancer cells.
Non-receptor Src tyrosine kinases (nrTKs) are overexpressed in a variety of human tumors, including cancer of the colon, breast, and pancreas, and their inhibitors are under intensive investigations as novel anti-tumor agents. However, these studies are not clear in the case of cervical cancer. Therefore, we studied the role of nrTKs and their inhibitors in the cervical cancer. The expression level of phospho-SrcY416 (pSrcY416) in several cervical cancer cell lines, normal cervical tissues, and cervical cancer tissues have been examined, and it has also been done whether PP2, an inhibitor of Src kinase, can inhibit the growth of cervical cells in vitro and in vivo. Immunohistochemical and confocal microscope studies suggested that pSrcY416 is overexpressed in HeLa and SiHa cells, as well as in the clinical cervical cancer tissues, compared to the normal cervical tissues. Down-regulation of pSrcY416 inhibited the cell proliferation by increasing the HeLa or SiHa cell population in the G0-G1 phase or S phase, respectively. Down-regulation of pSrcY416 led to up-regulation of p21Cip1 and p27Kip1 in both HeLa and SiHa cells and decreased the expression of cyclin A1, cyclin E, and cyclin-dependent kinase-2,-6 (CDK-2,-6) in HeLa cells and of cyclin B and CDK-2 in SiHa cells. Nude mice xenograft data showed that PP2 inhibited subcutaneous tumor growth significantly (P<0.05, compared with the control). Down-regulation of pSrcY416 contributes to cell growth inhibition in cervical cancer cells. nrTKs could therefore be a novel therapeutic targets for the treatment of cervical cancer.
Department of Biochemistry and Molecular Biology, Cancer Institute, Capital Medical University, and Fu Xing Hospital, No. 10 Xitoutiao, You An Men, 100069, Beijing, China.
Lu
L
Kong
Zhihong
Z
Deng
Yanzhong
Y
Zhao
Yamei
Y
Wang
Fazlul H
FH
Sarkar
Yuxiang
Y
Zhang
D000328:Adult; D000368:Aged; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002469:Cell Separation; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000473:pathology*; D023041:Xenograft Model Antitumor Assays; D019061:src-Family Kinases / Q000378:metabolism*
C412373:AG 1879; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D034741:RNA, Small Interfering; D019061:src-Family Kinases