[Antitumor and antimetastatic activities of plasmid pcDNA3. 1-IP10 complexed with cationic liposome in mice with 4T1 breast cancer].

Sichuan Da Xue Xue Bao Yi Xue Ban

National Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.

Published: March 2009

Objective: To determine the antitumor and antimetastatic effects of plasmid pcDNA3. 1-IP10 complexed with cationic liposome (DOTAP:CHOL) in mice with 4T1 breast cancer.

Methods: BALB/c mice model with 4T1 breast cancer was established. Thirty six mice with 4T1 breast cancers were divided randomly into three groups, which were intravenously injected with normal saline (200 microL), Lip-null (50 microg DNA, 200 microL) and Lip-IP10 (50 microg DNA, 200 microL) respectively every five days for six doses. The size of the tumors, the number of lung metastasis noduls and survival time were measured. Four mice from each group were sacrificed 43 days after tumor implantation. The tumor microvascula densities (MVD) were detected by immunohistochemical staining.

Results: Lip-IP10 inhibited the growth of tumor and the formation of lung metastasis neoplasm (P < 0.05). The Lip-IP10 group had a median of 3 lung metastasis nodules, less than the NS group (45) and Lip-null group (40) (P < 0.05). Lip-IP10 significantly prolonged the survival time of the tumor-bearing mice (P < 0.05). The histomorphometric analysis revealed a decreased MVD in the Lip-IP10 group (21.50 +/- 15.41 vs. 44.25 +/- 5.51 for the NS group and 43.45 +/- 4.21 for the Lip-null group, P < 0.05).

Conclusion: IP10 encapsulated in cationic liposome inhibits the growths and metastases of 4T1 breast cancers, which is based on the mechanism of IP10 inhibiting tumor angiogenesis.

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