Abstract
Docetaxel resistance developed in half of castration-resistant prostate cancer (CRPC) patients hinders its long-term clinical application. The current study was designed to investigate the effects of Chinese medicine Zhoushi Qi Ling decoction on the docetaxel resistance of prostate cancer as well as elucidate the underlying molecular mechanism. In our study, Qi Ling significantly decreased viability and colony formation as well as increased apoptosis of docetaxel-resistant (DR) CRPC cells. Qi Ling-treated DR cells exhibited decreased glucose consumption, lactate release and pyruvate production. Moreover, lncRNA SNHG10 was upregulated in DR tissues of CRPC patients and was negatively correlated with the progression-free survival. Bioinformatics analysis indicated miR-1271-5p as the associated miRNA possibly binding with SNHG10. miR-1271-5p up-regulation dramatically decreased the luciferase activity of SNHG10 in DR cells. SNHG10 knockdown sharply increased the expression of miR1271-5p in DR cells. Targetscan predicted TRIM66 as one of the downstream targets of miR-1271-5p. miR-1271-5p up-regulation drastically reduced luciferase activity as well as TRIM66 expression in DR cells. Also, the knockdown of SNHG10 remarkably suppressed the expression of TRIM66 in DR cells. Additionally, Qi Ling treatment reduced SNHG10 and TRIM66, while increased miR1271-5p, in DR cells. In summary, Qi Ling inhibited docetaxel resistance and glycolysis of CRPC possibly via SNHG10/miR-1271-5p/TRIM66 pathway.
Highlights
Despite dramatic progress in therapeutics having been made in recent years, prostate cancer remains one of the leading causes of cancer-related death in American men [1]
Colonies of docetaxelresistant cells in Qi Ling treated group were obviously decreased in the context of low-dose www.aging-us.com docetaxel compared with the untreated control cells, cosuggesting that Qi Ling suppressed proliferation of docetaxel-resistant castration-resistant prostate cancer (CRPC) cells when treated with docetaxel (Figure 1I)
Qi Ling-treated docetaxel-resistant CRPC cells showed decreased proliferation and increased apoptosis in the scenario of docetaxel treatment, indicating that Qi Ling enhanced the sensitivity of CRPC cells to docetaxel
Summary
Despite dramatic progress in therapeutics having been made in recent years, prostate cancer remains one of the leading causes of cancer-related death in American men [1]. While 50% of these ADT-treated patients can develop resistance to ADT, which eventually results in metastatic castration-resistant prostate cancer (CRPC). Cancer cells prefer to obtain energy via transferring glucose into lactate (aerobic glycolysis). This is a phenomenon termed “Warburg effect” which is essential to proliferation of cancer cells and patients’ prognosis prediction [6, 7]. This effect appears in prostate cancer cells [8,9,10]
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