Combination therapy of heparin-deoxycholic acid conjugate and doxorubicin against squamous cell carcinoma and B16F10 melanoma.
OBJECTIVE
Our previous study confirmed that heparin-deoxycholic acid conjugate (HD) had a potent antiangiogenic effect and safety to use for long-term treatment. Herein, the combined therapeutic effect of HD and doxorubicin (DOX) was evaluated against squamous cell carcinoma (SCC7) and B16F10 melanoma.


METHODS
The inhibitory effect of cell proliferation and cellular uptake of HD was studied in SCC7 and B16F10. The combination effects of HD and DOX were evaluated by measuring cytotoxicity and apoptosis as well as tumor growth and apoptosis in vivo against SCC7 and B16F10 tumor-bearing mice.


RESULTS
HD displayed potent inhibitory effect on SCC7 and B16F10 cell proliferation, but it showed a low cytotoxic effect. Concurrent treatment of HD and DOX displayed enhanced cytotoxic effects and apoptosis on SCC7 and B16F10. The cellular uptake of HD and DOX was affected by the collective cytotoxic effects of these two drugs: each drug suppressed the tumor growth, and their combined treatment enhanced apoptosis and collectively inhibited the tumor growth of SCC7 and B16F10 in vivo.


CONCLUSIONS
These results demonstrated that HD with cytostatic and antiangiogenetic activities, enhanced the antitumor activity of DOX against SCC7 and B16F10, and the combined treatment of these two drugs might have enhanced therapeutic efficacy.
Park
Kyeongsoon
K
Biomedical Research Center, Korea Institute of Science and Technology, 39-1 Hawolgok-dong, Seongbuk-gu, Seoul, 136-791, South Korea.
Lee
Gee Young
GY
Park
Rang-Woon
RW
Kim
In-San
IS
Kim
Sang Yoon
SY
Byun
Youngro
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D003840:Deoxycholic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005434:Flow Cytometry; D006493:Heparin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL
D003840:Deoxycholic Acid; D004317:Doxorubicin; D006493:Heparin