20(S)-protopanaxadiol inhibition of progression and growth of castration-resistant prostate cancer.
20(S)-protopanaxadiol inhibition of progression and growth of castration-resistant prostate cancer.
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20(S)-原人参二醇抑制去势抵抗性前列腺癌的进展和生长
DOI：
10.1371/journal.pone.0111201
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Dong Y
中科院分区：
文献类型：
--
作者：
Cao B;Qi Y;Yang Y;Liu X;Xu D;Guo W;Zhan Y;Xiong Z;Zhang A;Wang AR;Fu X;Zhang H;Zhao L;Gu J;Dong Y
雄激素剥夺治疗后前列腺癌的去势抵抗性进展仍然是前列腺癌临床管理中最关键的挑战。雄激素受体（AR）活性的恢复是去势抵抗性进展的既定驱动因素，全长AR（AR-FL）和组成型活性AR剪接变体（AR-Vs）的上调可能有助于AR活性的恢复。我们以前报道过，PPD可以降低AR-FL和AR-Vs的丰度。在本研究中，我们进一步表明PPD对AR表达和靶基因的影响不依赖于雄激素。PPD治疗导致配体非依赖性AR反式激活的抑制。此外，PPD延迟去势抵抗性再生长的LNCaP异种移植瘤雄激素剥夺后，抑制去势抵抗性22 Rv 1异种移植瘤的生长与内源性表达的AR-FL和AR-Vs。这是伴随着血清前列腺特异性抗原水平下降，以及减少AR水平和有丝分裂的肿瘤。值得注意的是，22 Rv 1异种移植肿瘤对下一代抗雄激素Enzalutamide的生长抑制具有抗性。本研究首次显示PPD在抑制去势抵抗性进展和前列腺癌生长方面的临床前疗效。这些发现为进一步开发PPD或其类似物用于前列腺癌治疗提供了理论基础。
Castration-resistant progression of prostate cancer after androgen deprivation therapies remains the most critical challenge in the clinical management of prostate cancer. Resurgent androgen receptor (AR) activity is an established driver of castration-resistant progression, and upregulation of the full-length AR (AR-FL) and constitutively-active AR splice variants (AR-Vs) has been implicated to contribute to the resurgent AR activity. We reported previously that ginsenoside 20(S)-protopanaxadiol-aglycone (PPD) can reduce the abundance of both AR-FL and AR-Vs. In the present study, we further showed that the effect of PPD on AR expression and target genes was independent of androgen. PPD treatment resulted in a suppression of ligand-independent AR transactivation. Moreover, PPD delayed castration-resistant regrowth of LNCaP xenograft tumors after androgen deprivation and inhibited the growth of castration-resistant 22Rv1 xenograft tumors with endogenous expression of AR-FL and AR-Vs. This was accompanied by a decline in serum prostate-specific antigen levels as well as a decrease in AR levels and mitoses in the tumors. Notably, the 22Rv1 xenograft tumors were resistant to growth inhibition by the next-generation anti-androgen enzalutamide. The present study represents the first to show the preclinical efficacy of PPD in inhibiting castration-resistant progression and growth of prostate cancer. The findings provide a rationale for further developing PPD or its analogues for prostate cancer therapy.
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影响因子：
82.9
作者：
Chen, CD;Welsbie, DS;Sawyers, CL
通讯作者：
Sawyers, CL
DOI：
10.1158/1078-0432.ccr-08-2660
发表时间：
2009-08-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Knudsen KE;Scher HI
通讯作者：
Scher HI
影响因子：
5.7
作者：
Dong, Y;Zhang, HT;Ip, C
通讯作者：
Ip, C
影响因子：
2.6
作者：
Lee, Nam-Hun;Yoo, Sa-Ra;Son, Chang Gue
通讯作者：
Son, Chang Gue
影响因子：
11.2
作者：
Hu R;Dunn TA;Wei S;Isharwal S;Veltri RW;Humphreys E;Han M;Partin AW;Vessella RL;Isaacs WB;Bova GS;Luo J
通讯作者：
Luo J