β-石竹烯(BCP),一种天然的双环倍半萜，是红辣椒和其他植物中丰富的生物分子。最近,据报道，它可以减少许多癌细胞的生长和增殖，并增强细胞凋亡，包括结直肠,卵巢,膀胱癌和肺癌.另一方面,顺铂（CDDP）与其他植物化学化合物的联合治疗协同增强了CDDP对几种癌症的杀伤作用。在当前模型中,我们已经测试了BCP在增强CDDP对肺癌细胞系的抗肿瘤活性中的作用。结果表明，BCP在中等剂量下是无毒的，并且在75µM以上的剂量下可以预防肺癌的进展。然而,当与CDDP结合时，BCP通过调节细胞周期改善化疗前的功能，细胞凋亡和EMT信号分子。基因和蛋白表达分析表明，CDDP和BCP联合治疗可显著上调细胞周期蛋白依赖性激酶抑制剂的水平，CDKN1A,和细胞凋亡的抑制剂，BCL-xl2.此外,联合治疗降低了凋亡调节剂的蛋白质水平，BCL-2.此外，BCP似乎抑制了与CDDP化疗相关的EMT过程，因为联合治疗诱导了CDDP治疗细胞中上皮细胞标志物E-cad水平的显着增加。同意这一点，联合治疗能够调节CDDP对间充质转录因子ZEB-2的作用.此外,已经进行了分子对接来检查BCP与这些和其他信号分子的虚拟相互作用，但只有细胞周期蛋白依赖性激酶CDK6被发现与BCP结合，在四个地点具有较高且稳定的吸引能量(-7.8)。一起,这些数据表明BCP通过调节细胞周期增强CDDP化疗功能，细胞凋亡和EMT信号分子。
Beta-Caryophyllene (BCP), a natural bicyclic sesquiterpenes, is an abundant biomolecule in red pepper and other plants. Recently, it was reported to reduce the growth and the proliferation as well as enhance the apoptosis in numerous cancer cells, including colorectal, ovarian, bladder cancer and lung cancer. On the other hand, the combination therapy of cisplatin (CDDP) with other phytochemical compounds has synergistically enhanced the killing effect of CDDP on several types of cancer. In the current model, we have tested the role of BCP in enhancing the anti-tumor activity of CDDP on lung cancer cell lines. The results showed that BCP is not toxic at moderate doses and it can prevent lung cancer progression in doses above 75 µM. However, when being combined with CDDP, BCP improved the former chemotherapeutic function through regulating cell cycle, apoptosis and EMT signaling molecules. Gene and protein expression analysis showed that the combined treatment of CDDP and BCP significantly upregulated the level of the cyclin-dependent kinase inhibitor, CDKN1A, and the inhibitor of the apoptosis, BCL-xl2. In addition, the combination treatment reduced the protein level of the apoptosis regulator, BCL-2. Moreover, BCP appears to prohibit the EMT process that is associated with CDDP chemotherapy since the combination treatment induced a significant increase in the level of the epithelial cell marker E-cad that was reduced in CDDP-treated cells. In agreement with that, the combined treatment managed to modulate the effect of CDDP on the mesenchymal transcription factor ZEB-2. Additionally, molecular docking has been conducted to check the virtual interaction of BCP with these and other signaling molecules, but only cyclin-dependent kinase CDK6 was found to virtually bind with BCP, and at four sites with higher and stable biding energy (-7.8). Together, these data indicate that BCP enhances CDDP chemotherapeutic function through regulating the cell cycle, the apoptosis and EMT signaling molecules.
