Elghali Fares, Msalbi Dhouha, Frikha Fakher, Alonazi Mona, Sahli Emna, Hakim Bochra, Mnif Sami, Ben Bacha Abir, Aifa Sami
Laboratory of Molecular and Cellular Screening Processes, Centre of Biotechnology of Sfax, B.P.1177, Sfax 3038, Tunisia.
Biochemistry Department, Science College, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia.
ACS Omega. 2024 Nov 26;9(49):48112-48124. doi: 10.1021/acsomega.4c04760. eCollection 2024 Dec 10.
Despite their wide usage in reducing tumors and improving patients' survival, chemotherapeutic drugs or natural compounds are facing the development of cancer resistance. Many experimental data and clinical trials have shown that combinatorial treatment could be an efficient solution for some resistance problems. In this study, we aimed to evaluate the synergistic effects of combining prodigiosin (PG), a natural compound with known anticancer properties, with the commonly used chemotherapy drugs 5-fluorouracil (5-FU), oxaliplatin, and paclitaxel. The primary objective was to identify the most potent combination that could enhance tumor cytotoxicity while minimizing drug resistance. experiments using three cancer cell lines (LoVo, HCT-116, and A549) were conducted to assess the impact of these combinations on the cell viability and proliferation. Recorded data demonstrated that the combination of 20 μM PG with 1/2 IC50 of 5-FU showed the most significant decrease in cell viability, with remaining viabilities of 28, 32, and 43% for LoVo, HCT-116, and A549 cells, respectively. This combination resulted in a notable increase in the proportion of cells in the G0/G1 phase and a decrease in the S phase of the cell cycle. These findings indicated that this combination effectively induced cell-cycle arrest. In contrast, other combinations such as PG with paclitaxel or oxaliplatin were less effective. Furthermore, molecular docking studies revealed that PG targets Akt1, a key protein in the PI3K/Akt survival pathway, providing a possible explanation for its proapoptotic effects. These findings suggested that the combination of PG with 5-FU enhanced tumor cell sensitivity to chemotherapy, potentially offering a more effective treatment strategy for overcoming drug resistance. In conclusion, the current study highlighted the promising potential of PG in combination with 5-FU as a therapeutic approach for colorectal and lung cancers, warranting further investigations in preclinical and clinical settings.
尽管化疗药物或天然化合物在缩小肿瘤和提高患者生存率方面有广泛应用，但它们正面临癌症耐药性的问题。许多实验数据和临床试验表明，联合治疗可能是解决某些耐药问题的有效方法。在本研究中，我们旨在评估具有已知抗癌特性的天然化合物灵菌红素（PG）与常用化疗药物5-氟尿嘧啶（5-FU）、奥沙利铂和紫杉醇联合使用的协同作用。主要目标是确定最有效的组合，既能增强肿瘤细胞毒性又能最小化耐药性。使用三种癌细胞系（LoVo、HCT-116和A549）进行实验，以评估这些组合对细胞活力和增殖的影响。记录的数据表明，20 μM PG与1/2 IC50的5-FU联合使用时，细胞活力下降最为显著，LoVo、HCT-116和A549细胞的剩余活力分别为28%、32%和43%。这种组合导致细胞周期中G0/G1期细胞比例显著增加，S期细胞比例下降。这些发现表明该组合有效地诱导了细胞周期停滞。相比之下，PG与紫杉醇或奥沙利铂等其他组合效果较差。此外，分子对接研究表明，PG靶向PI3K/Akt生存途径中的关键蛋白Akt1，这为其促凋亡作用提供了可能的解释。这些发现表明，PG与5-FU联合使用增强了肿瘤细胞对化疗的敏感性，可能为克服耐药性提供更有效的治疗策略。总之，当前研究突出了PG与5-FU联合作为结直肠癌和肺癌治疗方法的潜在前景，值得在临床前和临床环境中进一步研究。
