Combined time-restricted feeding and cisplatin enhance the anti-tumor effects in cisplatin-resistant and -sensitive lung cancer cells

作者全名："Li, Jianling; Chen, Qianyao; Shi, Dan; Lian, Xuemei"

作者地址："[Li, Jianling; Chen, Qianyao; Shi, Dan; Lian, Xuemei] Chongqing Med Univ, Sch Publ Hlth, Dept Nutr & Food Hyg, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China; [Li, Jianling; Chen, Qianyao; Shi, Dan; Lian, Xuemei] Chongqing Med Univ, Ctr Lipid Res, Key Lab Mol Biol Infect Dis, Minist Educ, Chongqing 400016, Peoples R China"

通信作者："Shi, D; Lian, XM (通讯作者)，Chongqing Med Univ, Sch Publ Hlth, Dept Nutr & Food Hyg, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China.; Shi, D; Lian, XM (通讯作者)，Chongqing Med Univ, Ctr Lipid Res, Key Lab Mol Biol Infect Dis, Minist Educ, Chongqing 400016, Peoples R China."

来源：MEDICAL ONCOLOGY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000905648300001

JCR分区：Q3

影响因子：3.4

年份：2022

卷号：40

期号：1

开始页：　

结束页：　

文献类型：Article

关键词：Time-restricted feeding; Cisplatin; Lung cancer; mRNA sequence; P53

摘要："Combination therapy as an important treatment option for lung cancer has been attracting attention due to the primary and acquired resistance of chemotherapeutic drugs in the clinical application. In the present study, as a new therapy strategy, concomitant treatment with time-restricted feeding (TRF) plus cisplatin (DDP) on lung cancer growth was investigated in DDP-resistant and DDP-sensitive lung cancer cells. We first found that TRF significantly enhanced the drug susceptibility of DDP in DDP-resistant A549 (A549/DDP) cell line, illustrated by reversing the inhibitory concentration 50 (IC50) values of A549/DDP cells to normal level of parental A549 cells. We also found that TRF markedly enhanced DDP inhibition on cell proliferation, migration, as well as promoted apoptosis compared to the DDP alone group in A549, H460 and A549/DDP cells lines. We further revealed that the synergistic anti-tumor effect of combined DDP and TRF was greater than that of combined DDP and simulated fasting condition (STS), a known anti-tumor cellular medium. Moreover, mRNA sequence analysis from A549/DDP cell line demonstrated the synergistic anti-tumor effect involved in upregulated pathways in p53 signaling pathway and apoptosis. Notably, compared with the DDP alone group, combination of TRF and DDP robustly upregulated the P53 protein expression without mRNA level change by regulating its stability via promoting protein synthesis and inhibiting degradation, revealed by cycloheximide and MG132 experiments. Collectively, our results suggested that TRF in combination with cisplatin might be an additional novel therapeutic strategy for patients with lung cancer."

基金机构：National Natural Science Foundation of China; CQMU Program for Youth Innovation in Future Medicine [NSFC81973030]; [W0085]

基金资助正文："This research was supported by the National Natural Science Foundation of China (NSFC81973030), CQMU Program for Youth Innovation in Future Medicine (No. W0085)."