title: A feasibility study on gene therapy of pancreatic carcinoma with Ad-PUMA.
abstract: Pancreatic cancer is one of the most malignant tumors with high mortality and poor prognosis even with the aggressive conventional therapies. Biotherapy based on the understanding of tumorigenesis mechanism is ongoing to improve the outcomes of cancer patients. We sought here to evaluate the therapeutic potential of a proapoptotic gene, PUMA, in pancreatic cancer. We found that PUMA was differently expressed in a series of pancreatic ductal adenocarcinoma cancer cell lines, and adenovirus-mediated expression of PUMA (Ad-PUMA) in these cells resulted in massive apoptosis. PUMA was more potent than p53 in suppressing growth of cancer cells. RT-PCR and Western Blot revealed that exogenous PUMA was expressed 6 h after Ad-PUMA infection. Furthermore, we assessed the efficacy of Ad-PUMA combining anticancer drugs (5-fluorouracil, cisplatin, gemcitabine hydrochloride, respectively) in these pancreatic cancer cell lines. Data revealed that PUMA significantly sensitized pancreatic carcinoma cell lines to chemotherapeutics, which may be resulted from abundant apoptosis induction. In nude mice with PANC-1 xenografts, Ad-PUMA treatment significantly inhibited the tumor growth. These results suggest that PUMA is a potent molecular tool in suppressing tumor growth sensitizing pancreatic carcinoma cells to chemical drugs. PUMA plays roles in negatively regulating cancer cell growth and may be a promising tool for cancer biotherapy, with or without combination with chemotherapeutic agents.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute/Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Haijuan
authors.initials: H
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Pei
authors.forename: Qingchun
authors.initials: Q
authors.lastname: Luan
authors.forename: Fei
authors.initials: F
authors.lastname: Ma
authors.forename: Shaohua
authors.initials: S
authors.lastname: Zhou
authors.forename: Zhilong
authors.initials: Z
authors.lastname: Zhao
authors.forename: Xiting
authors.initials: X
authors.lastname: Meng
authors.forename: Xueyan
authors.initials: X
authors.lastname: Zhang
authors.forename: Xiao
authors.initials: X
authors.lastname: Liang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Qimin
authors.initials: Q
authors.lastname: Zhan
authors.forename: Chen
authors.initials: C
authors.lastname: Lin
authors.forename: Haili
authors.initials: H
authors.lastname: Qian
authors.forename: Ping
authors.initials: P
authors.lastname: Zhao
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis / Q000235:genetics*; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002945:Cisplatin / Q000494:pharmacology; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D005240:Feasibility Studies; D005472:Fluorouracil / Q000494:pharmacology; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000473:pathology / Q000628:therapy*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics*; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D003841:Deoxycytidine; D002945:Cisplatin; D005472:Fluorouracil; D000093542:Gemcitabine