PI3K/AKT/mTOR pathway promotes progestin resistance in endometrial cancer cells by inhibition of autophagy

Endometrial cancer (EC) is now one of the most common malignant tumors in young women. In all, 90% of young patients with EC have a high expression of progesterone recep tor, can be treated with progestin, and have very good prognosis. However, some of the young EC patients are resistant to progesti...

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Bibliographic Details
Published in:OncoTargets and therapy 2017-01, Vol.10, p.2865-2871
Main Authors: Liu, Hua, Zhang, Liqin, Zhang, Xuyan, Cui, Zhumei
Format: Article
Language:English
Subjects:
Analysis
Breast cancer
Care and treatment
Cell growth
Cell proliferation
Drug therapy
Endometrial cancer
Kinases
Mutation
Original Research
Progestational hormones
Progesterone receptors
Prognosis
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Summary:Endometrial cancer (EC) is now one of the most common malignant tumors in young women. In all, 90% of young patients with EC have a high expression of progesterone recep tor, can be treated with progestin, and have very good prognosis. However, some of the young EC patients are resistant to progestin, the mechanism of which is unclear. To illuminate the mechanism by which endometrial cells acquire progestin resistance, we treated Ishikawa cells by slowly increasing dosage of progestin and established a progestin-resistant cell subline. We show here that progesterone resistant cells acquire increased proliferation rate and interestingly decreased autophagy. To uncover the mechanism by which cells increase proliferation and bypass autophagy, we found higher activation of phosphatidylinositol 3-kinase/AKT/mTOR signaling pathway was necessary to this malignant acquirement by RNAi technique. Further, we elucidated that activation of mTOR was sufficient and necessary for progestin resistance. RAD001, an inhibitor of mTOR, decreased phosphorylation of mTOR and inhibited proliferation of progestin-resistant cancer cells by promoting autophagy. Thus, our results indicated that mTOR can be a target to treat the progestin-resistant EC.
ISSN:1178-6930
1178-6930
DOI:10.2147/ott.s95267