Transfection of PDCD5 sensitizes colorectal cancer cells to cisplatin-induced apoptosis in vitro and in vivo.
This study was purposed to explore the mechanism of augmenting apoptosis-inducing effects of cisplatin on colorectal cancer SW480 cells by stable transfection of Programmed Cell Death 5 (PDCD5) gene, both in vitro and in vivo. The expression level of PDCD5 of SW480 cells stably transfected with PDCD5 (SW480/PDCD5) and pcDNA3.1/Neo(+) empty vector stably transfected cells (SW480/Neo) was examined by real-Time RT-PCR and Western blot. The effects of cisplatin in combination with PDCD5 on the proliferation and apoptosis of colorectal cancer cells were measured by using MTT analysis, Hoechst 33258 analysis and flow cytometry with Annexin-V-FITC/PI dual labeling, respectively. To examine the combination therapeutic effect of PDCD5 and cisplatin, tumor xenograft model was prepared for in vivo study. The results showed that PDCD5 levels of SW480/PDCD5 were higher than SW480 and SW480/Neo, respectively. The PDCD5 enhanced the apoptotic percentage of SW480/PDCD5 cells induced by cisplatin, as compared SW480 and SW480/Neo, respectively. In in vivo study, the transfection of PDCD5 increased the efficacy of cisplatin-induced inhibition of tumor growth in nude mice. It is concluded that stable transfection of PDCD5 gene can notably improve apoptosis-inducing effects of cisplatin on colorectal cancer cells, which is a novel strategy to better chemotherapeutic effects on colorectal cancer.
Yin
Anning
A
Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei Province, People's Republic of China.
Jiang
Yingan
Y
Zhang
Xianfeng
X
Zhao
Juan
J
Luo
Hesheng
H
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D015316:Genetic Therapy; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism* / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
D051017:Apoptosis Regulatory Proteins; D009363:Neoplasm Proteins; C117283:PDCD5 protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins; D002945:Cisplatin