Qi Ling decoction enhances abiraterone treatment via suppression of autophagy in castration resistant prostate cancer

Abstract

Abiraterone acetate has exhibited impressive results in improving progression-free survival of patients with metastatic castration-resistant prostate cancer. However, many patients may develop abiraterone resistance with a variable duration of response. Hence, identifying a remedy to overcome abiraterone resistance is critical for patients with castration-resistant prostate cancer. In this study, we aim to explore the potential of Qi Ling decoction (QLD), a traditional Chinese medicine, in attenuating abiraterone resistance in prostate cancer. Cell viability and apoptosis were respectively measured by Cell Counting Kit-8 (CCK-8) assay and flow cytometry. The protein levels were assessed by Western blotting assay. Autophagosome formation was quantified by counting LC3 puncta. We found that QLD was capable of promoting abiraterone-induced apoptosis and cell death of PC3-AbiR and DU145-AbiR cells in vitro. A combination of QLD and abiraterone yielded a better tumor inhibition effect than QLD alone and abiraterone alone. Further investigation revealed that QLD restored the abiraterone sensitivity of PC3-AbiR and DU145-AbiR cells through modulating autophagy. These findings suggest that QLD might serve as a potential remedy to enhance the therapeutical effect of abiraterone for patients with castration-resistant prostate cancer.

Chrysosplenol D can inhibit the growth of prostate cancer by inducing reactive oxygen species and autophagy

“… 22 To explore the regulatory mechanism of autophagy in prostate cancer and develop related drugs for autophagy may provide a new method for the treatment of prostate cancer. 23 We also revealed that CHD affected the progression of prostate cancer by suppressing autophagy. In addition, oxidative stress is related to the occurrence of prostate hyperplasia and prostate cancer.…”

“…In the process of tumor pathogenesis, autophagy plays a “double‐sided role,” which can not only fight cancer but also promote cancer development 22 . To explore the regulatory mechanism of autophagy in prostate cancer and develop related drugs for autophagy may provide a new method for the treatment of prostate cancer 23 . We also revealed that CHD affected the progression of prostate cancer by suppressing autophagy.…”

“…Autophagy also plays an important role in the treatment of prostate cancer. Therefore, both inflammation and autophagy play an important role in prostate cancer, and CHD inhibits prostate cancer progression mainly by affecting inflammation and autophagy 23 …”

“…Therefore, both inflammation and autophagy play an important role in prostate cancer, and CHD inhibits prostate cancer progression mainly by affecting inflammation and autophagy. 23 The limitation of this study is the lack of in-depth mechanism research, and the next step is to systematically investigate the signaling pathway through which CHD affects prostate cancer. Relevant downstream proteins and pathways can be analyzed in combination with proteomics and transcriptomics and validated at the cellular and animal levels.…”

Making the Case for Autophagy Inhibition as a Therapeutic Strategy in Combination with Androgen-Targeted Therapies in Prostate Cancer

“…Recently, Feng et al [51] studied Qi Ling decoction (QLD), a Chinese herb, in combination with abiraterone using PC-3 and DU145 cells that were developed to be abiraterone resistant. Using flow cytometry and CCK-8 assays, QLD in combination with abiraterone resulted in decreased cell survival together with robust apoptosis in the resistant cell lines as compared to each drug alone.…”