title: Knockdown of Hypoxia-Inducible Factor 1α Improved the Efficacy of Low-Dose Metronomic Chemotherapy of Paclitaxel in Human Colon Cancer Xenografts.
abstract: Low-dose metronomic chemotherapy represents a new strategy for solid tumor treatments with a strong antiangiogenic activity and few side effects. However, low-dose metronomic therapy alone is not always as effective as traditional chemotherapy on eradication of tumor. On the contrary, low-dose metronomic in some cases could stimulate tumor growth due to hypoxia of tumor cells induced during therapy. Our study aimed to investigate whether knockdown of hypoxia-inducible factor-1α expression in tumor cell could facilitate low-dose metronomic therapy with paclitaxel for human colon cancer. Human colon cancer cell line (HT-29) stably transfected with specific short hairpin RNAs silencing hypoxia-inducible factor-1α exhibited marked attenuation of hypoxia-induced expression of the target genes such as vascular endothelial growth factor, glucose transporter 1, and P-glycoprotein. Compared with HT-29-c xenograft tumor model established by subcutaneous injection of HT-29 cells stably transfected with scrambled control short hairpin RNA, HT-29-ih xenograft tumor model showed more significant and long-lasting antitumor responses of empirical metronomic paclitaxel regimens, accompanied by drastic angiogenesis decrease and neglectable toxicity. All these data indicated that the combination of paclitaxel low-dose metronomic therapy with hypoxia-inducible factor-1α knockdown might provide a potent battle against colon cancer.
authors: 1 Department of Emergency, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors: Mu
authors: M
authors: Zhang
authors: 2 Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors: Chen
authors: C
authors: Chen
authors: 1 Department of Emergency, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors: Feng
authors: F
authors: Su
authors: 1 Department of Emergency, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors: Zhiguo
authors: Z
authors: Huang
authors: 1 Department of Emergency, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors: Xiangmin
authors: X
authors: Li
authors: 1 Department of Emergency, Xiangya Hospital, Central South University, Changsha, Hunan, People's Republic of China.
authors: Xiaogang
authors: X
authors: Li
mesh_terms: D059250:Administration, Metronomic; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000009:adverse effects; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000235:genetics; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; D017239:Paclitaxel
keywords: HIF-1α knockdown; LDM; angiogenesis; apoptosis; cell proliferation; invasion; side effects