title: Overexpression of SOX2 is involved in paclitaxel resistance of ovarian cancer via the PI3K/Akt pathway.
abstract: Paclitaxel is recommended as a first-line chemotherapeutic agent against ovarian cancer, but drug resistance becomes a major limitation of its success clinically. The key molecule or mechanism associated with paclitaxel resistance in ovarian cancer still remains unclear. Sex-determining region Y-box 2 (SOX2) is of vital importance in the regulation of stem cell proliferation and carcinogenesis. The aim of this study was to evaluate the role of SOX2 in ovarian cancer tumorigenesis and paclitaxel resistance. In the present study, the expression of SOX2 was examined by immunohistochemistry (IHC) and real-time PCR in 40 clinical samples and in SKOV3 cells and SKOV3/TAX cells (paclitaxel-resistant human ovarian adenocarcinoma cell line). The effects of SOX2 knockdown on ovarian cancer cell proliferation, migration, and invasion were also studied. The IHC and real-time PCR results showed that the difference of SOX2 expression between ovarian cancer and the adjacent non-tumorous ovarian tissues was statistically significant. Western blot analysis revealed that the PI3K/Akt signaling pathway was inhibited in cells overexpressing SOX2. Western blot analysis showed that the SOX2 protein was overexpressed in paclitaxel-resistant cells and weakly detectable in paclitaxel-sensitive cells. SOX2 silencing significantly potentiated apoptosis induced by paclitaxel in SKOV3-TR with SOX2 knockdown compared to SKOV3-TR transfected with control small interfering RNA (siRNA). Our work indicates SOX2 will become both a rational indicator of ovarian cancer prognosis and a promising target for ovarian cancer gene therapy.
authors.affiliation: Department of Obstetrics and Gynecology, Zhengzhou University People's Hospital, No. 8 Weft Five Road, Jinshui District, Zhengzhou, Henan, 450003, China. drliyang666@163.com.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Scientific Research Office, The Affiliated Cancer Hospital Zhengzhou University People's Hospital, Zhengzhou, 450008, China.
authors.forename: Kangdong
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Gynecology Oncology, The Affiliated Cancer Hospital Zhengzhou University People's Hospital, Zhengzhou, 450008, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Zhengzhou University People's Hospital, No. 8 Weft Five Road, Jinshui District, Zhengzhou, Henan, 450003, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Obstetrics and Gynecology, Zhengzhou University People's Hospital, No. 8 Weft Five Road, Jinshui District, Zhengzhou, Henan, 450003, China.
authors.forename: Juxin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Gynecology Oncology, The Affiliated Cancer Hospital Zhengzhou University People's Hospital, Zhengzhou, 450008, China. drrenwu6@163.com.
authors.forename: Wu
authors.initials: W
authors.lastname: Ren
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009367:Neoplasm Staging; D051058:Oncogene Protein v-akt / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D055748:SOXB1 Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt; D017239:Paclitaxel
keywords: Apoptosis; Chemoresistance; Ovarian cancer; Proliferation; SKOV3/TAX cells; SOX2