Zou Ting, Liu Jun-Yan, Liu Zhao-Qian, Xiao Di, Chen Juan
Department of Pharmacy, National Institution of Drug Clinical Trial, Xiangya Hospital, Central South University, Changsha 410008, China.
Hunan Key Laboratory of Pharmacogenetics, Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China.
Pharmaceuticals (Basel). 2024 Aug 24;17(9):1118. doi: 10.3390/ph17091118.
Lung cancer has the highest fatality rate among malignant tumors in the world. Finding new biomarkers of drug resistance is of great importance in the prognosis of lung cancer patients. We found that the polymorphisms of Adenylate Cyclase 1 (ADCY1) are significantly associated with platinum-based chemotherapy resistance in lung cancer patients in our previous research. In this study, we wanted to identify the mechanism of ADCY1 affecting platinum resistance. We used an MTT assay to find if the expression of ADCY1 is associated with the sensitivity of cisplatin in A549, H1299, and A549-DDP cells. Then, we performed CCK-8 tests to detect the absorbance of these cells stimulated by ADCY1, which can discover the cell proliferation that is affected by ADCY1. We investigated cell apoptosis and cell cycles regulated by ADCY1 through the flow cytometry assay. RNA sequencing was used to find the downstream genes affected by ADCY1 which may be associated with drug resistance in lung cancer patients. ADCY1 has higher expression in lung cancer cells than in normal cells. ADCY1 can affect cisplatin resistance in lung cancer cells by regulating cell proliferation, cell apoptosis, and the cell cycle. It may control cell apoptosis by regulating the classical apoptosis biomarkers Bax and Bcl2. Our study showed that ADCY1 may be a new biomarker in the prognosis of lung cancer patients. Much work remains to be carried out to clarify the mechanism in this important emerging field.
肺癌是全球恶性肿瘤中死亡率最高的。寻找新的耐药生物标志物对肺癌患者的预后至关重要。我们在先前的研究中发现，腺苷酸环化酶1（ADCY1）的多态性与肺癌患者对铂类化疗的耐药性显著相关。在本研究中，我们想确定ADCY1影响铂耐药性的机制。我们使用MTT法来检测ADCY1的表达是否与顺铂在A549、H1299和A549-DDP细胞中的敏感性相关。然后，我们进行CCK-8试验以检测受ADCY1刺激的这些细胞的吸光度，这可以发现受ADCY1影响的细胞增殖情况。我们通过流式细胞术检测ADCY1调控的细胞凋亡和细胞周期。RNA测序用于寻找受ADCY1影响的下游基因，这些基因可能与肺癌患者的耐药性有关。ADCY1在肺癌细胞中的表达高于正常细胞。ADCY1可通过调节细胞增殖、细胞凋亡和细胞周期来影响肺癌细胞对顺铂的耐药性。它可能通过调节经典凋亡生物标志物Bax和Bcl2来控制细胞凋亡。我们的研究表明，ADCY1可能是肺癌患者预后的一种新生物标志物。在这个重要的新兴领域，仍有许多工作需要开展以阐明其机制。
