PO.CH01.05 · 化学
一种生物活性大麻来源提取物REPYR-SC1对前列腺癌的剂量依赖性抗增殖活性
Dose-dependent anti-proliferative activity of a bioactive hemp-derived extract REPYR-SC1 against prostate cancer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
在美国,约每8名男性中就有1名被诊断为前列腺癌,而转移性病例占前列腺癌相关死亡的大部分。前列腺癌是男性癌症死亡的第二大原因,5年生存率为32%。目前的治疗采用雄激素剥夺疗法、雄激素信号受体抑制剂和化疗的联合方案。尽管有这些进步,去势抵抗和化疗抵抗仍是持续缓解的重大障碍,表明需要新的治疗方法。免疫疗法和新型抗肿瘤药物的发现是当前备受关注的治疗方式。鉴于临床前证据表明大麻素衍生物具有抗肿瘤疗效及潜在免疫活性,我们探索使用一种新型大麻提取物REPYR-SC1作为抗癌、免疫调节剂。使用C4细胞建立前列腺癌模型,HPrEC前列腺上皮细胞作为非癌性对照,并选择CTLL-2细胞毒性T淋巴细胞作为免疫调节能力的可量化指标。REPYR-SC1以0、0.1、0.5、1和5 μL/mL的剂量给药,并与C4、HPrEC和CTLL-2细胞培养24和48小时。在处理前后通过光学显微镜进行形态学评估。随后进行处理前后的手动细胞计数,继而进行台盼蓝排斥实验。细胞计数仅纳入存活细胞。REPYR-SC1在前列腺癌C4细胞和CTLL-2细胞中产生了显著的剂量和时间依赖性增殖降低(p<0.001)。在1和5 μL/mL剂量下,于24和48小时时,C4细胞的增殖被完全抑制。HPrEC细胞表现出极低的敏感性,在48小时5 μL/mL下仅观察到20%的抑制。CTLL-2细胞表现出显著的敏感性,在48小时1和5 μL/mL剂量下观察到增殖被完全抑制。REPYR-SC1在体外对T淋巴细胞表现出可测量的免疫调节作用,并对前列腺癌细胞表现出选择性抗肿瘤活性。总之,REPYR-SC1显示出抑制前列腺癌的潜力证据,值得进一步研究。
查看英文原文 English abstract
In the US approximately 1 in 8 men are diagnosed with prostate cancer, and metastatic cases account for the majority of prostate cancer-related mortality. Prostatic cancer is the second leading cause of cancer death in men, harboring a 32% 5-year survival rate. Current treatments utilize a combination of androgen deprivation therapy, androgen signaling receptor inhibitors and chemotherapy. Despite these improvements, castration-resistance and chemotherapy resistance remain a significant obstacle to sustained remission and signify a need for novel therapeutic approaches. Immunotherapies and the discovery of new anti-neoplastic agents are current modalities of considerable interest. We explore the use of REPYR-SC1, a novel hemp extract, as an anti-cancer, immunomodulatory agent following the pre-clinical evidence demonstrating anti-neoplastic efficacy of cannabinoid derivatives and their potential immunoactivity. C4 cells were used to model prostate cancer, HPrEC prostate epithelial cells as a non-cancerous control, and CTLL-2 cytotoxic T lymphocytes were chosen as a quantifiable measure of immunomodulatory capability. REPYR-SC1 was administered at 0, 0.1, 0.5, 1, and 5 μL/mL and cultured with C4, HPrEC and CTLL-2 cells for 24 and 48 hours. Morphological assessment was performed by light microscopy, pre- and post-treatment. Subsequent to this manual cell counts were performed pre-and post-treatment, followed by trypan blue exclusion assay. Only viable cells were included in the cell count. REPYR-SC1 produced a significant dose- and time-dependent reduction in proliferation (p<0.001) in prostate cancer C4 cells and CTLL-2 cells. At a dose of 1 and 5 μL/mL at the 24- and 48-hour mark, full inhibition of proliferation was observed in C4 cells. HPrEC cells showed minimal susceptibility with 20% inhibition observed for 5 μL/mL at 48 hours. CTLL-2 cells showed significant susceptibility with complete inhibition of proliferation observed at a dose of 1 and 5 µL/mL at 48 hours. REPYR-SC1 exhibited measurable immunomodulatory effects against T-lymphocytes in vitro, and selective anti-neoplastic activity versus prostate cancer cells. In conclusion, REPYR-SC1 demonstrated evidence of potential for prostate cancer inhibition and warrants further investigation.
利益披露 Disclosure
J. Costoya, None..
J. J. Jimenez, None.