Evaluation of the effects of androgenic Chinese herbal medicines on androgen receptors and tumor growth in experimental prostate cancer models.

ETHNOPHARMACOLOGICAL RELEVANCE: Many prostate cancer (PCa) patients in Mainland China and other Asian countries often use Chinese herbal medicines as an adjuvant treatment while receiving Western medicines. However, concerns have been raised about the potential herb-drug interaction when using herbal medicines containing phytoandrogens. AIM OF THE STUDY: This study aimed to investigate the effects of the selected 21 Chinese herbal medicines on the proliferation and tumor growth using the relevant in vitro and in vivo models of PCa. MATERIALS AND METHODS: After treatment of LNCaP and 22Rv1 cells with different concentrations of 70% ethanol extracts of the 21 selected herbal medicines for 48 h, the proliferative activity, the effects on androgen receptor (AR) and prostate specific antigen (PSA) were determined. The anti-tumor effects of the 21 herbs on PCa growth were also investigated on a subcutaneous mouse model of PCa. RESULTS: The results showed that Epimedii Folium (EF) and Codonopsis Radix (CNR) could significantly increase the cell viability in LNCaP cells (p < 0.05 for both) and 22Rv1 cells (p < 0.05 for both), protein expressions of AR in LNCaP cells (p < 0.05 for both) and 22Rv1 cells (p < 0.05 for both), and PSA (p < 0.05 for both) in LNCaP cells. EF, CNR, and Cistanches Herba (CCH) markedly accentuated the tumor growth (p < 0.05 for three drugs) and AR expression (p < 0.05 for three herbs) in tumor tissues. On the other hand, treatment with Astragali Radix (AGR), Chuanxiong Rhizoma (CXR) and Bruceae Fructus (BF) significantly inhibited the cell viability in LNCaP cells (p < 0.05, p < 0.05 and p < 0.001, respectively) and in 22Rv1 cells (p < 0.05, p < 0.05 and p < 0.001, respectively), and the protein expression of AR in LNCaP cells (p < 0.05 for three herbs) and 22Rv1 cells (p < 0.05, p < 0.05 and p < 0.001, respectively), and the protein expression of PSA (p < 0.05 for three herbs) in LNCaP cells, as well as tumor growth (p < 0.05 for three herbs) and the AR expression (p < 0.05 for AGR and CXR, p < 0.001 for BF) in tumor tissues. CONCLUSION: Our results revealed that AGR, CXR and BF suppressed the PCa development via inhibition of AR expression, while EF, CNR and CCH promoted the development and progression of PCa via enhancement of AR expression. The results strongly suggest that caution should be exercised when using androgenic Chinese herbal medicines in PCa patients.

Impact of RNAi targeting survivin gene on tumor growth, apoptosis and radiosensitivity in nude mice xenograft of human cervical carcinoma / 中国癌症杂志

Background and purpose: Recently, survivin gene is one of the hot spots in tumor study. The purpose of the present study was to observe the impact of RNAi targeting survivin gene on tumor growth, apoptosis and radiosensitivity in nude mice xenograft of human cervical carcinoma. Methods: HeLa-s2, HeLa-NC, HeLa-U6 neo and HeLa cells were inoculated respectively in flank subcutaneous tissue of 24 female nude mice so as to establish xenograft models of human cervical carcinoma randomly. The tumor growth status was observed. The tumor volume was regularly measured and the tumor weight was investigated used to observe the impact of RNAi targeting survivin gene on tumor growth. The expression of survivin protein and FⅧRAg in tumor tissues were examined by immunohistochemistry SP method MVD was calculated. Cell apoptusis in tumor tissues was observed by HE staining,apoptotic index(AI) was quantified by TUNEL method. To observe the impact of RNAi targeting survivin gene on tumor radiosensitivity after irradiated, the tumor growth delay and tumor weight were investigated and cell apoptosis were examined by TUNEL method. Results: We established 4 groups of xenograft models of human cervical carcinoma.The tumor volume of HeLa-s2 group was obviously less than that of HeLa group at every checkpoint. The tumor weight of HeLa-s2 group was obviously lower than that of HeLa group, and they were(0.369±0.043)g and (1.150±0.136)g respectively(P<0.05).The tumor growth inhibitive rate of HeLa-s2 group was 67.9%. The expression of survivin protein FⅧ RAg examined by immunohistochemistry in tumor tissues of HeLa-s2 group decreased sharply and MVD went down to 23.4±3.1. Apoptotic cells increased in tumor tissues of HeLa-s2 group examined by HE staining and TUNEL method, AI was (22.74±1.4)%. The tumor volume of HeLa-s2 group was obviously less than that of HeLa group at every checkpoint after irradiation and the tumor weight of HeLa-s2 group was obviously lower than that of HeLa group, they were:(0.41±0.06)g and(1.38±0.29)g respectively(P<0.05). Cell apoptosis increased in tumor tissues of HeLa-s2 group.Compared with HeLa group, AI of HeLa-s2 group rose up notably, they were(30.06±0.98)% and (4.17±0.64)%(P<0.05).Conclusion: RNAi for survivin gone can reduce MVD in xenograft by inhibiting survivin protein expression, thus inhibit tumor growth and induce cell apoptosis, Survivin gene RNAi can also enhance tumor radiosensitivity.