COMP-Ang1 potentiates the antitumor activity of 5-fluorouracil by improving tissue perfusion in murine Lewis lung carcinoma.
Chemotherapy is often hindered by abnormal tumor vascularity, which causes impaired delivery of drugs into the tumor. Angiopoietin-1 has potent roles in angiogenesis and vessel maturation. We report here that an angiopoietin-1 variant, COMP-Ang1, promotes vascular remodeling and pericyte coverage and thereby promotes the efficient delivery of a chemotherapeutic drug into tumors of murine Lewis lung carcinoma. The combination of COMP-Ang1 with the cytotoxic drug 5-fluorouracil potentiated the effect of 5-fluorouracil on tumor growth without increasing animal toxicity. Moreover, COMP-Ang1 increased perfusion into the tumor. Although COMP-Ang1 increased the functional vasculature in the tumor, COMP-Ang1 alone did not promote tumor growth, possibly due to its promotion of increased pericyte coverage. This study suggests that COMP-Ang1 may improve the microcirculation within a tumor by increasing functional vasculature and tissue perfusion and that the combination of chemotherapy together with COMP-Ang1 might be an advantageous therapeutic approach.
Hwang
Jeong-Ah
JA
Department of Physiology, College of Medicine, Chungnam National University, 6 Munhwa-dong, Jung-gu, Daejeon 301-131, Republic of Korea.
Lee
Eun Hui
EH
Kim
Hyun-Woo
HW
Park
Jin Bong
JB
Jeon
Byeong Hwa
BH
Cho
Chung-Hyun
CH
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D018827:Carcinoma, Lewis Lung / Q000098:blood supply* / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010477:Perfusion; D020286:Pericytes / Q000187:drug effects / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; C515576:COMP-Ang1 fusion protein; D011993:Recombinant Fusion Proteins; D005472:Fluorouracil