Department of Life Science and Agroforestry, Qiqihar University, Qiqihar, Heilongjiang 161006, P.R. China.
Mol Med Rep. 2020 Sep;22(3):1793-1802. doi: 10.3892/mmr.2020.11263. Epub 2020 Jun 22.
Toosendanin (TSN) is a tetracyclic triterpenoid extracted from Melia toosendan Sieb, et Zucc, which primarily grows in specific areas of China. Although toosendanin (TSN) exerts antitumoral effects on various human cancer cells, its influence on gastric cancer (GC) is remains to be elucidated. MicroRNAs (miRNAs/miRs) serve crucial roles in apoptosis and proliferation of cancer cells. miR‑23a‑3p has been shown to be associated with human GC; however, the specific function of miR‑23a‑3p in GC remains unclear. Therefore, the present study aimed to elucidate the role of miR‑23a‑3p in the regulation of GC cell proliferation and apoptosis induced in vitro by TSN treatment. Subsequently, apoptosis‑related genes expression levels were quantified by reverse transcription‑quantitative PCR and western blot analysis, respectively, and the target relationship between miR‑23a‑3p and BCL2 was determined by luciferase reporter gene analysis. Additionally, cell proliferation and apoptosis experiments were carried out. The results indicated that TSN inhibited proliferation and induced apoptosis in MKN‑45 cells. Moreover, it upregulated the expression of miR‑23a‑3p. B‑cell lymphoma‑2 (BCL2) was identified as a potential target gene of miR‑23a‑3p, which was demonstrated to bind to the 3'‑untranslated region of BCL2 mRNA, as detected by the luciferase reporter assay. Further studies revealed that BCL2 expression was downregulated following overexpression of miR‑23a‑3p. In addition, the overexpression of the miR‑23a‑3p inhibited proliferation, induced G1 arrest and increased apoptosis in MKN‑45 cells. The results of the present study demonstrated that miR‑23a‑3p inhibited proliferation and induced apoptosis of GC cells, which may be attributable to its direct targeting of BCL2. These results may provide a novel insight into the apoptosis of GC cells, and may lead to investigations into the mechanisms of the effects of TSN.
川楝素（TSN）是从川楝 Melia toosendan Sieb，et Zucc 中提取的四环三萜类化合物，主要生长在中国的特定地区。虽然川楝素（TSN）对各种人类癌细胞具有抗肿瘤作用，但它对胃癌（GC）的影响仍有待阐明。microRNAs（miRNAs/miRs）在癌细胞的凋亡和增殖中发挥着关键作用。miR-23a-3p 已被证明与人类 GC 相关；然而，miR-23a-3p 在 GC 中的具体功能尚不清楚。因此，本研究旨在阐明 miR-23a-3p 在 TSN 处理体外诱导的 GC 细胞增殖和凋亡中的作用。随后，通过逆转录-定量 PCR 和 Western blot 分析分别定量检测凋亡相关基因的表达水平，并通过荧光素酶报告基因分析确定 miR-23a-3p 与 BCL2 之间的靶关系。此外，进行了细胞增殖和凋亡实验。结果表明，TSN 抑制 MKN-45 细胞的增殖并诱导其凋亡。此外，它上调了 miR-23a-3p 的表达。B 细胞淋巴瘤-2（BCL2）被鉴定为 miR-23a-3p 的潜在靶基因，通过荧光素酶报告基因分析证实其与 BCL2 mRNA 的 3'非翻译区结合。进一步的研究表明，BCL2 表达在 miR-23a-3p 过表达后下调。此外，miR-23a-3p 的过表达抑制 MKN-45 细胞的增殖，诱导 G1 期阻滞并增加其凋亡。本研究结果表明，miR-23a-3p 抑制 GC 细胞的增殖并诱导其凋亡，这可能归因于其对 BCL2 的直接靶向作用。这些结果可能为 GC 细胞的凋亡提供新的见解，并可能导致对 TSN 作用机制的研究。
