Medical Biochemistry Department, Medical Research Division, National Research Centre, Dokki, 12622, Cairo, Egypt.
Cancer Biology and Genetics Laboratory, Centre of Excellence for Advanced Sciences, National Research Centre, Dokki 12622, Cairo, Egypt.
Anticancer Agents Med Chem. 2019;19(18):2197-2210. doi: 10.2174/1871520619666190930123520.
The clinical application of cisplatin is limited by severe side effects associated with high applied doses. The synergistic effect of a combination treatment of a low dose of cisplatin with the natural alkaloid α-solanine on human hepatocellular carcinoma cells was evaluated.
HepG2 cells were exposed to low doses of α-solanine and cisplatin, either independently or in combination. The efficiency of this treatment modality was evaluated by investigating cell growth inhibition, cell cycle arrest, and apoptosis enhancement.
α-solanine synergistically potentiated the effect of cisplatin on cell growth inhibition and significantly induced apoptosis. This synergistic effect was mediated by inducing cell cycle arrest at the G2/M phase, enhancing DNA fragmentation and increasing apoptosis through the activation of caspase 3/7 and/or elevating the expression of the death receptors DR4 and DR5. The induced apoptosis from this combination treatment was also mediated by reducing the expression of the anti-apoptotic mediators Bcl-2 and survivin, as well as by modulating the miR-21 expression.
Our study provides strong evidence that a combination treatment of low doses of α-solanine and cisplatin exerts a synergistic anticancer effect and provides an effective treatment strategy against hepatocellular carcinoma.
顺铂的临床应用受到与高应用剂量相关的严重副作用的限制。评估低剂量顺铂与天然生物碱α-茄碱联合治疗对人肝癌细胞的协同作用。
将 HepG2 细胞暴露于低剂量的α-茄碱和顺铂中，单独或联合使用。通过研究细胞生长抑制、细胞周期阻滞和凋亡增强来评估这种治疗方式的效率。
α-茄碱与顺铂协同增强了对细胞生长抑制的作用，并显著诱导了凋亡。这种协同作用是通过诱导细胞周期阻滞在 G2/M 期、增强 DNA 片段化以及通过激活 caspase 3/7 和/或上调死亡受体 DR4 和 DR5 来增加凋亡来介导的。这种联合治疗诱导的凋亡也通过降低抗凋亡介质 Bcl-2 和 survivin 的表达以及调节 miR-21 的表达来介导。
我们的研究提供了强有力的证据表明，低剂量α-茄碱和顺铂的联合治疗具有协同的抗癌作用，并为治疗肝癌提供了有效的治疗策略。
