Ultrasonically Enhanced ZD2767P-Carboxypeptidase G2 Deactivates Cisplatin-Resistant Human Lung Cancer Cells

作者全名："Liu, Qianfen; Li, Xinya; Luo, Yuanyuan; Wang, Houmei; Zhang, Ying; Yu, Tinghe"

作者地址："[Liu, Qianfen] Chongqing Med Univ, Women & Childrens Hosp, Chongqing Hlth Ctr Women & Children, Dept Obstet & Gynecol, Chongqing, Peoples R China; [Liu, Qianfen; Li, Xinya; Luo, Yuanyuan; Wang, Houmei; Zhang, Ying; Yu, Tinghe] Chongqing Med Univ, Affiliated Hosp 2, Chongqing, Peoples R China"

通信作者："Zhang, Y; Yu, TH (通讯作者)，Chongqing Med Univ, Affiliated Hosp 2, Chongqing, Peoples R China."

来源：OXIDATIVE MEDICINE AND CELLULAR LONGEVITY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000885042500001

JCR分区：Q2

影响因子：7.31

年份：2022

卷号：2022

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："The prodrug-enzyme regimen ZD2767P+CPG2 is limited by low efficacy. Here, ultrasound was used to modulate ZD2767P+CPG2 (i.e., ZD2767P+CPG2+US) against cisplatin-resistant human lung cancer cells. A549 and A549/DDP (resistant subline) cells received ZD2767P+CPG2 or ZD2767P+CPG2+US. Either ZD2767P+CPG2 or ZD2767P+CPG2+US led to cell death and apoptosis, and ZD2767P+CPG2+US produced stronger effects; comet assays revealed that these two means directly caused DNA double-strand break. Z-VAD-fmk and/or ferrostatin-1 increased the cell survival percentage, and Z-VAD-fmk decreased the apoptosis percentage. The level of transferrin was increased in treated cells, but those of ferroportin and glutathione peroxidase 4 (GPX4) were reduced, with higher intracellular levels of reactive oxygen species and of iron. Intracellular pharmacokinetics of ZD2767D (activated drug) indicated that the peak level, area under the drug level vs. time curve, and mean residence time in ZD2767P+CPG2+US were higher than those in ZD2767P+CPG2. Both ZD2767P+CPG2 and ZD2767P+CPG2+US were effective on xenograft tumors in nude mice; inhibitory rates were 39.7% and 63.5% in A549 tumors and 50.0% and 70.1% in A549/DDP tumors, respectively. A higher apoptosis level and a lower GPX4 level were noted in tumors receiving treatments. No severe adverse events were observed. These data demonstrated that ZD2767P+CPG2+US deactivated cancer cells via apoptosis and ferroptosis pathways, being a candidate therapy for cisplatin-resistant lung cancer."

基金机构："Second Affiliated Hospital, Chongqing Medical University [2017-74]"

基金资助正文："This work was supported by The Second Affiliated Hospital, Chongqing Medical University (2017-74)."