Synergistic antitumor effect of CXCL10 with hyperthermia.
OBJECTIVE
IFN-inducible protein 10 (IP-10)/CXCL10 (CXC chemokine ligand 10) has been described as an antiangiogenic chemokine and displays a potent antitumor activity in vivo. In the present study, we try to investigate whether the combination therapy of hyperthermia, a physical antiangiogenic modality, with CXCL10 would completely eradicate the established solid tumors.


METHODS
Immunocompetent BALB/c mice bearing Meth A fibrosarcoma were established. Mice were treated with either CXCL10 at 25 microg/kg once a day for 20 days, hyperthermia was given twice (at 42 degrees C for 1 h, on day 6 and 12 after the initiation of CXCL10), or together. Tumor volume and survival time were observed. The microvessel density was determined by CD31 immunofluorescence. Histologic analysis and assessment of apoptotic cells were also conducted in tumor tissues.


RESULTS
The results showed that CXCL10 and hyperthermia inhibited the growth of Meth A fibrosarcoma and interestingly, the combination therapy enhanced the antiangiogenic effects and completely eradicated the established solid tumors. Histological examination revealed that CXCL10 + hyperthermia led to increased induction of apoptosis, tumor necrosis, and elevated lymphocyte infiltration compared with the controls. Moreover, the tumor eradicated animals developed a protective T-cell-dependent antitumor memory response against Meth A tumor cells rechallenge.


CONCLUSIONS
Our finding is that the combination therapy can achieve a synergistic antitumor efficacy, supporting the idea that the combination of two antiangiogenic agents may lead to improved clinical outcome. These findings could open new perspectives in clinical antitumor therapy.
Chen
Ping
P
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, 1# Keyuan Road 4, Gaopeng Street, High Technological Development Zone, Chengdu, Sichuan 610041, People's Republic of China.
Yang
Ling-Lin
LL
Yang
Han-Shuo
HS
Wang
Yong-Sheng
YS
Li
Gang
G
Wu
Yang
Y
Fang
Fang
F
Liu
Kang
K
Li
Jie
J
Zhao
Xia
X
Hu
Huo-Zhen
HZ
Wei
Yu-Quan
YQ
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis; D045744:Cell Line, Tumor; D054357:Chemokine CXCL10 / Q000009:adverse effects / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D006360:Heat-Shock Proteins / Q000502:physiology; D006979:Hyperthermia, Induced; D007156:Immunologic Memory; D051379:Mice; D008807:Mice, Inbred BALB C; D012513:Sarcoma, Experimental / Q000098:blood supply / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013601:T-Lymphocytes / Q000276:immunology
D020533:Angiogenesis Inhibitors; D054357:Chemokine CXCL10; D006360:Heat-Shock Proteins