[Preparation and biological activity of poly (gamma-glutamic acid) -cisplatin conjugate].
Preparation of a poly (gamma-glutamic acid)-cisplatin conjugate was introduced and its in vitro antitumor effect was investigated. Poly (gamma-glutamic acids) was obtained by using fermentation methods. The hydrolyzed small molecular weight of poly (gamma-glutamic acids) was prepared by acid hydrolysis. The interaction between poly (gamma-glutamic acids) -cisplatin conjugate (PGA-CDDP) and DNA was investigated by PCR model. MTT assay was used to investigate the in vitro anticancer activity of the conjugate. Apoptosis assay of the conjugate was investigated by FCM assay and the in vivo toxicity was also proceeded. The results showed that the poly (gamma-glutamic acids) -cisplatin conjugate was obtained successfully and its yield is 10% - 12%. It has obvious antitumor effects on human liver tumor BEL7404 cells, human lung tumor H446 cells and human colon tumor RKO cells. At the same time, it also has apoptosis effects on the three kinds of tumor cell lines. The in vivo toxicity of PGA-CDDP was examined in normal mice and the results showed that the in vivo toxicity of this conjugate was significantly lower than that of free CDDP. In conclusion, the poly (gamma-glutamic acids) -cisplatin conjuate could be used as a potential clinic antitumor drug. The poly (gamma-glutamic acids) obtained by fermentation can be used as a valuable drug carrier system.
Jin
Li
L
School of Life Science, East China Normal University, Shanghai 200062, China.
Ye
Hai-Feng
HF
Huang
Jing
J
Jiang
Lin
L
Hu
Rong-Zhang
RZ
Wu
Zi-Rong
ZR
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000494:pharmacology*; D004337:Drug Carriers; D005260:Female; D005285:Fermentation; D006863:Hydrogen-Ion Concentration; D008297:Male; D051379:Mice; D011099:Polyglutamic Acid / Q000008:administration & dosage* / Q000494:pharmacology
D000970:Antineoplastic Agents; D004337:Drug Carriers; D011099:Polyglutamic Acid; D002945:Cisplatin