Administration of PUMA adenovirus increases the sensitivity of esophageal cancer cells to anticancer drugs.
Esophageal cancer is one of the most lethal human tumors, characterized by relative chemoresistance and poor prognosis. Researchers have been seeking for multimodality to improve its outcome of therapy. PUMA (p53 upregulated modulator of apoptosis) is a potent proapoptotic molecule that is rapidly induced in cells following DNA damage and is required for p53-induced apoptosis. We evaluated the therapeutic potential of PUMA adenovirus against esophageal cancer cell lines (KYSE-150, KYSE-410, KYSE-510 and YES-2). Infection with Ad-PUMA (PUMA Adenovirus) resulted in the more powerful cytotoxicity in these cell lines compared with Ad-p53. Furthermore, we assessed the efficacy of a combined treatment with Ad-PUMA and anticancer drug (cisplatin, paclitaxel, 5-fluorouracil, respectively) for these cells and found PUMA significantly increased the chemosensitivity of esophageal cancer cells, which may result from more abundant apoptosis induction. Interestingly, Ad-PUMA was found to be more efficient than Ad-p53 in inhibiting cell growth and enhancing the chemosensitivity of esophageal cancer cell lines irrespective of the p53 status. These results suggest that Ad-PUMA is a potent cytotoxic agent and could be a promising alternative in the cancer gene therapy in combination with chemotherapeutic agents.
State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medicine Sciences & Peking Union Medical College, Beijing, China.
Haijuan
H
Wang
Haili
H
Qian
Jian
J
Yu
Xueyan
X
Zhang
Lin
L
Zhang
Ming
M
Fu
Xiao
X
Liang
Qimin
Q
Zhan
Chen
C
Lin
D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D017209:Apoptosis; D045744:Cell Line, Tumor; D002469:Cell Separation; D002470:Cell Survival; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000628:therapy; D005434:Flow Cytometry; D016158:Genes, p53; D006801:Humans; D016089:Immunodeficiency Virus, Feline / Q000378:metabolism*; D020128:Inhibitory Concentration 50; D010641:Phenotype; D011379:Prognosis; D012680:Sensitivity and Specificity
D000970:Antineoplastic Agents