Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Center for Innovative Clinical Medicine, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
Curr Gene Ther. 2020;20(1):64-70. doi: 10.2174/1566523220666200309125709.
We previously demonstrated that the reduced expression in immortalized cells (REIC)/dikkopf-3 (Dkk-3) gene was downregulated in various malignant tumors, and that an adenovirus vector carrying the REIC/Dkk-3 gene, termed Ad-REIC induced cancer-selective apoptosis in pancreatic cancer and hepatocellular carcinoma.
In this study, we examined the therapeutic effects of Ad-REIC in biliary cancer using a second- generation Ad-REIC (Ad-SGE-REIC).
Human biliary cancer cell lines (G-415, TFK-1) were used in this study. The cell viability and apoptotic effect of Ad-SGE-REIC were assessed in vitro using an MTT assay and Hoechst staining. The anti-tumor effect in vivo was assessed in a mouse xenograft model. We also assessed the therapeutic effects of Ad-SGE-REIC therapy with cisplatin. Cell signaling was assessed by Western blotting.
Ad-SGE-REIC reduced cell viability, and induced apoptosis in biliary cancer cell lines via the activation of the c-Jun N-terminal kinase pathway. Ad-SGE-REIC also inhibited tumor growth in a mouse xenograft model. This effect was further enhanced in combination with cisplatin.
Ad-SGE-REIC induced apoptosis and inhibited tumor growth in biliary cancer cells. REIC/Dkk-3 gene therapy using Ad-SGE-REIC is an attractive therapeutic tool for biliary cancer.
我们之前的研究表明，在各种恶性肿瘤中，永生化细胞（REIC）/dikopf-3（Dkk-3）基因的表达减少，携带 REIC/Dkk-3 基因的腺病毒载体，称为 Ad-REIC，可诱导胰腺癌和肝细胞癌的癌症选择性凋亡。
本研究采用第二代 Ad-REIC（Ad-SGE-REIC），研究 Ad-REIC 在胆管癌中的治疗作用。
本研究使用人胆管癌细胞系（G-415、TFK-1）。采用 MTT 法和 Hoechst 染色法检测 Ad-SGE-REIC 对细胞活力和凋亡的影响。在小鼠异种移植模型中评估体内抗肿瘤作用。还评估了 Ad-SGE-REIC 联合顺铂治疗的疗效。通过 Western blot 检测细胞信号转导。
Ad-SGE-REIC 通过激活 c-Jun N-末端激酶通路降低胆管癌细胞系的细胞活力，并诱导其凋亡。Ad-SGE-REIC 还抑制了小鼠异种移植模型中的肿瘤生长。与顺铂联合使用时，这种作用进一步增强。
Ad-SGE-REIC 诱导胆管癌细胞凋亡并抑制肿瘤生长。使用 Ad-SGE-REIC 的 REIC/Dkk-3 基因治疗是胆管癌的一种有吸引力的治疗工具。
