Aim: To investigate whether microRNA-21 was involved in mediating the chemoresistance of prostate cancer cells to docetaxel. Methods: A microarray technique was used to determine the miRNA profile in docetaxel-resistant PC3 cells. Real-time PCR was used to confirm the array results. miR-21 mimics and inhibitors were synthesized and introduced to cells using Lipofectamine 2000. Cell proliferation was examined with the CCK-8 assay. Luciferase reporter containing PDCD 3′UTR was constructed and the activity was detected by a dual luciferase assay. PDCD4 protein expression was evaluated using Western blot. Results: A docetaxel-resistant prostate cancer PC3 cell line (PC3R) was established . Using microarrays, miR-21 was found to be upregulated in PC3R cells. Ectopic expression of miR-21 increased the resistance to docetaxel in PC3 wild type cells. In contrast, silencing of miR-21 in PC3R cells sensitized the cells to docetaxel. The IC 50 values for miR-21-silencing cells and control cells were 28.31 and 35.89 nmol/L, respectively. PDCD4, a direct target gene of miR-21, could mediate chemoresistance to docetaxel in PC3 cells. Conclusion: Our findings suggest that miR-21 contributed to the resistance of PC3 cells to docetaxel, and that targeting miR-21 may offer a promising therapeutic approach in sensitizing prostate cancer to docetaxel treatment.
During surgeries, the concentration of PM(2.5) could reach a very unhealthy status, especially for the chief surgeon who is the nearest to the incision site. Surgical smoke evacuation in the first few seconds of a cut is essential; however, using smoke evacuators such as a wall suction alone may not be enough.
OBJECTIVE
To evaluate the activation level of the mammalian target of rapamycin (mTOR) signalling pathway in Chinese patients with prostate cancer, as this pathway is over‐activated in many human cancers and is an attractive target for cancer therapy.
PATIENTS AND METHODS
We used immunohistochemistry to investigate the activation level of five important markers of the mTOR pathway, including PTEN, p‐Akt, p‐mTOR, p‐p70S6K and p‐4E‐BP1, in tissues from 182 patients with prostate cancer, 20 with benign prostatic hyperplasia (BPH) and 10 with high‐grade prostatic intraepithelial neoplasia (HGPIN). The expression levels of these five markers were associated with patient clinical and pathological characteristics.
RESULTS
Expression levels of p‐Akt, p‐mTOR, p‐4E‐BP1 and p‐p70S6K were significantly higher in prostate cancer tissues than in BPH and HGPIN tissues. In 182 patients with prostate cancer the p‐mTOR expression level significantly and positively correlated with its upstream p‐Akt and downstream p‐4E‐BP1 and p‐p70S6K expression levels. The cancer Gleason score was significantly correlated with p‐Akt and p‐mTOR expression level but not with p‐4E‐BP1 and p‐p70S6K expression level. However, the p‐4E‐BP1and p‐p70S6K expression levels in primary cancer lesions were statistically significantly correlated with patient T stage and distant metastases.
CONCLUSIONS
Most patients with prostate cancer have at least one component of the mTOR signalling pathway activated. The activation of the mTOR pathway might be involved in prostate cancer development and progression. The association between activation of mTOR pathway and patient clinicopathological variables suggested that not all patients are equally amenable to treatment strategies targeting the mTOR pathway.
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