Abstract

Qianlie Xiaozheng decoction (QLXZD), a traditional Chinese medicinal formula, has been used clinically to treat advanced prostate cancer (PCa) for more than 10 years. However, experimental evidence supporting its efficacy is lacking. Here, we investigated the anticancer properties and molecular mechanism of QLXZD in vitro in a human PCa cell line (PC3) and in vivo using PC3 xenografts in nude mice. We confirmed the antineoplastic activity of QLXZD by analyzing cell viability and tumor volume growth, which decreased significantly compared to that of the controls. Autophagy following QLXZD treatment was detected morphologically using transmission electron microscopy and was confirmed by measuring the expression of autophagy markers (LC3-II and p62) using fluorescence analysis, flow cytometry, and western blotting. Increasing autophagic flux induced by QLXZD was monitored via pmCherry-GFP-LC3 fluorescence analysis. QLXZD-induced autophagic cell death was alleviated by the autophagy inhibitors, 3-methyl adenine and hydroxychloroquine. We evaluated the total expression and phosphorylation levels of proteins involved in the Akt/mTOR pathway regulating autophagy. Phosphorylation of Akt, mTOR, and p70S6K, but not total protein levels, decreased following treatment. This is the first study to demonstrate the autophagy-related mechanistic pathways utilized during QLXZD-mediated antitumor activity both in vitro and in vivo. These findings support the clinical use of QLXZD for PCa treatment.

Highlights

  • Prostate cancer is one of the most prevalent malignant tumors as well as the second leading cause of cancer-related deaths in men in Western countries, with appropriately 15% of men having prostate cancer (PCa) during their lifetime (Kar et al, 2016)

  • We examined the mechanism of Qianlie Xiaozheng decoction (QLXZD) in vitro using the PC3 cell line

  • We demonstrate that QLXZD has antitumor capabilities and induces autophagy in PC3 cells in vitro and in PC3 xenografts in vivo with no overt toxicity

Read more

Summary

Introduction

Prostate cancer is one of the most prevalent malignant tumors as well as the second leading cause of cancer-related deaths in men in Western countries, with appropriately 15% of men having PCa during their lifetime (Kar et al, 2016). A treatment for PCa, shows obvious effects at the beginning of treatment, but after 14–30 months, most patients develop HIPC. Evidence shows that autophagy plays a key role in PCa development, and numerous studies focusing on potential anticancer treatments are ongoing (Naponelli et al, 2015; Amaravadi et al, 2016). Studies performed in epithelial PCa cells showed that autophagy may provide a survival mechanism in the prostate (Naponelli et al, 2015). Together, these data paradoxically indicate that induction or inhibition of autophagy could have effects against PCa, depending on context

Objectives
Methods
Results
Discussion
Conclusion
Full Text
Published version (Free)

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call