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α-蒎烯通过调控 miR-34a-5p/Bcl-2 信号轴的活性诱导细胞凋亡从而抑制宫颈癌的生长。

α-Pinene inhibits the growth of cervical cancer cells through its proapoptotic activity by regulating the miR-34a-5p/Bcl-2 signaling axis.

机构信息

School of Nursing, Guangdong Pharmaceutical University, Guangdong, China.

School of Pharmacy, Guangdong Pharmaceutical University, Guangdong, China.

出版信息

Drug Dev Res. 2022 Dec;83(8):1766-1776. doi: 10.1002/ddr.21994. Epub 2022 Sep 8.

Abstract

Among gynecological tumors, cervical cancer (CC) has the second-highest prevalence and mortality rate. α-Pinene is a bicyclic monoterpenoid compound extracted from pine needles that carried promising anticancer properties. Nevertheless, its effect on CC and the underlying mechanism has not yet been elucidated. Therefore, we investigated the effect of α-Pinene on apoptosis in CC via in vitro assays of flow cytometry (FCW), terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) assay, quantitative real-time polymerase chain reaction (qRT-PCR), and Western blot. Following that, we detected the proapoptotic function of α-Pinene on HeLa cells in vivo by TUNEL assay and immunofluorescence staining. Our results displayed that the α-Pinene inhibited the growth of HeLa cells and stalled the cells in the G0/G1 phase. Interestingly, we also detected that α-Pinene induced HeLa cells to apoptosis. The results investigated that α-Pinene induced HeLa cells apoptosis along with up-regulating the expression of Bax, Bid, caspase-9, caspase-3, miR-34a-5p, and down-regulating the expression of Bcl-2 in vitro. At the same time, the expression levels of target genes in vivo were consistent with those in vitro. Our experiment proved that α-Pinene promoted apoptosis, which will be used to hopefully maximize the therapeutic strategies in clinical studies in CC.

摘要

在妇科肿瘤中,宫颈癌(CC)的发病率和死亡率居第二位。α-蒎烯是从松针中提取的一种双环单萜化合物,具有有前景的抗癌特性。然而,其对 CC 的影响及其潜在机制尚未阐明。因此,我们通过流式细胞术(FCW)、末端脱氧核苷酸转移酶介导的缺口末端标记(TUNEL)检测、实时定量聚合酶链反应(qRT-PCR)和 Western blot 体外实验研究了 α-蒎烯对 CC 细胞凋亡的影响。之后,我们通过 TUNEL 检测和免疫荧光染色检测了α-蒎烯在体内对 HeLa 细胞的促凋亡作用。我们的研究结果显示,α-蒎烯抑制了 HeLa 细胞的生长,并使细胞停滞在 G0/G1 期。有趣的是,我们还发现 α-蒎烯诱导了 HeLa 细胞凋亡。研究结果表明,α-蒎烯通过上调 Bax、Bid、caspase-9、caspase-3、miR-34a-5p 的表达,下调 Bcl-2 的表达,诱导 HeLa 细胞凋亡。同时,体内靶基因的表达水平与体外一致。我们的实验证明了 α-蒎烯促进了细胞凋亡,这有望使 CC 临床研究中的治疗策略最大化。

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