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Archive > Volume 24 Issue 6 > 2017,24(6):601-607. DOI:10.3872/j.issn.1007-385X.2017.06.005 Prev Next
Basic Research
IL6 induces tamoxifen resistance in ovarian cancer cells through PI3K/Akt pathway
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Abstract:
Objective:This study aimed to explore the mechanism of tamoxifen (TAM) resistance caused by IL6 in ovarian cancer cells. Methods: Human ovarian cancer A2780 cell line that endogenously overexpressing IL6 and human ovarian cancer CAOV3 cell line that exogenously depleting IL6 were constructed; exogenous IL6 (50 ng/ml) were used for pretreatment of A2780 cells (A2780/perIL6 cells), and Western blotting was used to detect the effect of endogenous/exogenous IL6 on the phosphorylation level of ERα Ser167 in ovarian cancer cells; IL6 and/or Wortmannin (PI3K inhibitor) were used to treat A2780 cells and western blotting was used to detect their effect on the phosphorylation of Akt and ERα; MTT assay was used to detect the effect of Wortmannin and endogenous/exogenous IL6 on the sensitivity of A2780 cells to TAM; luciferase reporter assay was performed to detect transcription activity of ERα in ovarian cancer cells, and to explore the possible signaling pathway. Results: Both exogenous and endogenous overexpression of IL6 could obviously increase the level of ERα Ser167 phosphorylation in A2780 cells (all P<0.01), while endogenous depletion of IL6 could reduce the level of ERα Ser167 phosphorylation in CAOV3 cells (P<0.01). It also found that wortmannin (PI3K inhibitor) could significantly antagonize IL6induced TAM resistance and phosphorylation of ERα Ser167. IL6 promoted ERa transcription activity, while this activation was not blocked by the PI3Kspecific inhibitor wortmannin. Conclusion: These results indicate that IL6 could induce ERa phosphorylation by triggering PI3K/Akt signaling pathway to activate the ER pathway, and thereby induce the resistance of ovarian cancer cells to TAM.
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Project Supported:
Project supported by the National Natural Science Foundation of China (No. 81273520,No.81502256), the Great Program of the Science Foundation of Tianjin (No. 12JCZDJC26300), and the Great Program for Science and Technology in Logistics College of Chinese People’s Armed Police Forces (No. 2015 ZXKF05, No.WHB201404, No.WHB201406)
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