Suppressed protein expression of the death-associated protein kinase enhances 5-fluorouracil-sensitivity but not etoposide-sensitivity in human endometrial adenocarcinoma cells.
Targeted knockdown of the death-associated protein kinase (DAPK) expression in the endometrial adenocarcinoma HHUA cells reportedly induces cell death by enhancing the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis in an autocrine/paracrine manner. This suggests that endogenous DAPK is a potential candidate for a molecularly targeted anticancer therapy for patients with endometrial adenocarcinoma. To investigate the role of endogenous DAPK in anticancer drug sensitivity, we examined effects on cellular anticancer drug sensitivities of transfections with 5 different specific DAPK small-interfering RNAs (siRNAs) into HHUA cells. DAPK siRNA transfections strongly enhanced 5-fluorouracil (5FU)-sensitivity, but not etoposide-sensitivity, of HHUA cells compared with control siRNA-transfected cells. These results indicate that etoposide-stimulated cell death signals may share or include TRAIL-mediated apoptotic signals, and that 5FU-stimulated cell death signals may be independent from TRAIL-mediated apoptotic signals induced by DAPK siRNA transfections. Moreover, 5FU-combined chemotherapy with DAPK siRNA transfection may show stronger anticancer effects on patients with endometrial adenocarcinoma than does chemotherapy alone.
Tanaka
Tetsuji
T
Department of Obstetrics and Gynecology, Wakayama Medical University, Wakayama 641-0012, Japan. obgywmu@wakayama-med.ac.jp
Bai
Tao
T
Yukawa
Kazunori
K
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D045744:Cell Line, Tumor; D064550:Death-Associated Protein Kinases; D004354:Drug Screening Assays, Antitumor; D016889:Endometrial Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D005047:Etoposide / Q000494:pharmacology*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D055785:Gene Knockdown Techniques; D006801:Humans; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D014162:Transfection
D000964:Antimetabolites, Antineoplastic; D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D034741:RNA, Small Interfering; D005047:Etoposide; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D005472:Fluorouracil