Temozolomide/PLGA microparticles plus vatalanib inhibits tumor growth and angiogenesis in an orthotopic glioma model.
Temozolomide (TM) has anti-tumor activity in patients with malignant glioma. Implantable poly (D,L-lactide-co-glycolide) (PLGA) microparticles of TM (TM-MS) have been developed, enhancing the cytotoxicity of TM to Glioma C6 cells. Vatalanib, as anti-angiogenic agent, has also shown anti-tumor activity with malignant gliomas. We examined the combined effects of TM-MS and vatalanib in a rat orthotopic glioma model and found TM-MS offered a greater tumor inhibition than TM, and combination treatment with both of them improved the survival time versus single agent therapy. The combination treatment also demonstrated an inhibition to rat glioma tumors, a significant decrease in cell proliferation, an increase in apoptosis, and a lower microvessel density within the glioma tumors. The results suggest that TM-MS can more effectively inhibit tumor than TM, and combination treatment with TM-MS and vatalanib inhibits tumor growth and angiogenesis and may prove to be a promising therapy for malignant gliomas.
Zhang
Yu-Hui
YH
Department of Neurosurgery, Second Military Medical University, Shanghai, China.
Yue
Zhi-Jian
ZJ
Zhang
He
H
Tang
Gu-Sheng
GS
Wang
Yang
Y
Liu
Jian-Min
JM
D020533:Angiogenesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D019344:Lactic Acid; D008297:Male; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010793:Phthalazines / Q000494:pharmacology / Q000627:therapeutic use*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077204:Temozolomide; D016896:Treatment Outcome
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D010793:Phthalazines; D011725:Pyridines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C404768:vatalanib; D003606:Dacarbazine; D000077204:Temozolomide