Abstract
Objective To study the biological characteristics of paclitaxel resistant endometrial carcinoma cells and its mechanism of drug resistance. Method The paclitaxel resistant cell lines were established by high-dose paclitaxel (TAX) injection. The IC50 of paclitaxel was determined by CCK-8 assay in Ishikawa and Ishikawa-TAX. The cell cycle and apoptosis rate were detected by flow cytometry. Western blot was used to detect the expression of p-AKT and p-p70S6K. The expression of drug resistance-related genes Pgp and MDR1 was determined by RT-PCR. Cell viability was determined by soft agarose assay and invasive ability in vitro by transwell assay. Results Paclitaxel and NVP-BEZ235 cotreatment group can further inhibit the clonogenicity and invasion of Ishikawa and Ishikawa-TAX cells compared with paclitaxel alone and NVP-BEZ235 treatment group. Paclitaxel and NVP-BEZ235 cotreated groups increased the apoptosis rate of Ishikawa and increased G0/G1 phase arrest in both cells. Paclitaxel alone significantly inhibited p-AK and p-p70 S6K protein expression in Ishikawa and Ishikawa-TAX cells and the inhibition was enhanced by NVP-BEZ235 when cotreated with paclitaxel. Conclusion Paclitaxel can inhibit Ishikawa and Ishikawa-TAX cell via PI3K/Akt/mTOR signaling pathway. Paclitaxel and NVP-BEZ235 cotreatment can enhance the inhibitory effect.
Highlights
Endometrial cancer is one of the most common gynecologic malignancies
Endometrial cancer is a malignant tumor which originates from endometrial glands with a high incidence
It accounts for 20%-30% of the female reproductive system malignant tumors, which seriously endangers women’s health and life [14, 15]
Summary
Endometrial cancer is one of the most common gynecologic malignancies. The mortality is increasing because of the lack of no effective treatment for advanced and recurrent endometrial cancer, which seriously affects the quality of life of women [1, 2]. Chemotherapy is the primary method of treatment [3]. The combination of paclitaxel/taxol (TAX) and platinum compounds is the first-line chemotherapy regime for endometrial cancer, which shows a certain effect on primary endometrial cancer [4]. With the extension of dosage and duration, the induced paclitaxel resistance often leads to the failure of chemotherapy in endometrial carcinoma [6]. The study of drug resistance in endometrial cancer is of great significance for clinical treatment, especially for the advanced and recurrent endometrial cancer
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