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大麻二酚和大麻素作为一种潜在的治疗方法,可用于体外沉默 RBBP6 和 PC3 异种移植的前列腺癌细胞。

Cannabidiol and Cannabis Sativa as a potential treatment in vitro prostate cancer cells silenced with RBBp6 and PC3 xenograft.

机构信息

Department of Biochemistry, University of Johannesburg, Auckland Park Campus, Johannesburg, South Africa.

出版信息

Mol Biol Rep. 2023 May;50(5):4039-4047. doi: 10.1007/s11033-022-08197-0. Epub 2023 Feb 28.

DOI:10.1007/s11033-022-08197-0
PMID:36853473
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10147767/
Abstract

BACKGROUND

Prostate cancer is the second most frequently occurring carcinoma in males worldwide and one of the leading causes of death in men around the world. Recent studies estimate that over 1.4 million males are diagnosed with prostate cancer on an annual basis, with approximately 375,000 succumbing to the disease annually. With current treatments continuing to show severe side effects, there is a need for new treatments. In this study we looked at the effect of cannabis sativa extract, cannabidiol and cisplatin on prostate cancer cells, PC3.

METHODS

In addressing the above questions, we employed the MTT assay to measure the antiproliferative effect on PC3 cells following treatment with varying concentrations of Cannabis sativa extract, cisplatin and cannabidiol. xCELLigence was also used to confirm the IC50 activity in which cells were grown in a 16 well plate coated with gold and monitor cell attachment. Caspase 3/7 activity was also measured using 96 well-plate following treatment. Western-blot and qRT-PCR was also used to measure the gene expression of tumour suppressor genes, p53, Bax and Bcl2. Animal studies were employed to measure the growth of PC3-mouse derived cancer to evaluate the effect of compounds in vivo.

RESULTS

From the treatment with varying concentrations of Cannabis sativa extract, cannabidiol and cisplatin, we have observed that the three compounds induced antiproliferation of PC3 cancer cell lines through the activation of caspase 3/7 activity. We also observed induction of apoptosis in these cells following silencing of retinoblastoma binding protein 6 (RBBP6), with upregulation of p53 and bax mRNA expression, and a reduction in Bcl2 gene expression. The growth of tumours in the mouse models were reduced following treatment with cisplatin and cannabidiol.

CONCLUSION

We demonstrated that cannabidiol is a viable therapy to treat prostate cancer cells, in combination with silencing of RBBP6. This suggests that cannabidiol rather Cannabis sativa extract may play an important role in reducing cancer progression.

摘要

背景

前列腺癌是全球男性第二大常见癌种,也是全球男性死亡的主要原因之一。最近的研究估计,每年有超过 140 万男性被诊断出患有前列腺癌,每年约有 37.5 万人因此病去世。由于目前的治疗方法继续显示出严重的副作用,因此需要新的治疗方法。在这项研究中,我们研究了大麻素提取物、大麻二酚和顺铂对前列腺癌细胞 PC3 的影响。

方法

为了解决上述问题,我们采用 MTT 法检测不同浓度的大麻素提取物、顺铂和大麻二酚处理 PC3 细胞后的抗增殖作用。还使用 xCELLigence 确认 IC50 活性,即细胞在涂有金的 16 孔板中生长并监测细胞附着。用 96 孔板检测细胞处理后 caspase 3/7 的活性。还使用 Western blot 和 qRT-PCR 测量肿瘤抑制基因 p53、Bax 和 Bcl2 的基因表达。进行动物研究以测量 PC3-衍生的小鼠癌症的生长,从而评估化合物在体内的作用。

结果

从不同浓度的大麻素提取物、大麻二酚和顺铂处理中,我们观察到三种化合物通过激活 caspase 3/7 活性诱导 PC3 癌细胞系的增殖抑制。我们还观察到这些细胞中的细胞凋亡诱导,在沉默视网膜母细胞瘤结合蛋白 6 (RBBP6) 后,p53 和 bax mRNA 表达上调,Bcl2 基因表达下调。顺铂和大麻二酚治疗后,小鼠模型中的肿瘤生长减少。

结论

我们证明大麻二酚是一种可行的治疗前列腺癌细胞的方法,与沉默 RBBP6 联合使用。这表明大麻二酚而不是大麻素提取物可能在降低癌症进展方面发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b74/10147767/364e0482c684/11033_2022_8197_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b74/10147767/8498e26ef036/11033_2022_8197_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b74/10147767/70db3046915b/11033_2022_8197_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b74/10147767/6310e5f2160a/11033_2022_8197_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b74/10147767/e03f068b6c20/11033_2022_8197_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b74/10147767/364e0482c684/11033_2022_8197_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b74/10147767/8498e26ef036/11033_2022_8197_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b74/10147767/70db3046915b/11033_2022_8197_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b74/10147767/6310e5f2160a/11033_2022_8197_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b74/10147767/e03f068b6c20/11033_2022_8197_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0b74/10147767/364e0482c684/11033_2022_8197_Fig5_HTML.jpg

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