antitumor activity of noscapine in combination with doxorubicin in triple negative breast cancer诺司卡品结合阿霉素的抗肿瘤活性三阴性乳腺癌.pdf

Antitumor Activity of Noscapine in Combination with Doxorubicin in Triple Negative Breast Cancer 1 2 2 2 Mahavir B. Chougule , Apurva R. Patel , Tanise Jackson , Mandip Singh * 1 College of Pharmacy, University of Hawaii, Hilo, Hawaii, United States of America, 2 College of Pharmacy, Florida AM University, Tallahassee, Florida, United States of America Abstract Background: The aim of this study was to investigate the anticancer activity and mechanism of action of Noscapine alone and in combination with Doxorubicin against triple negative breast cancer (TNBC). Methods: TNBC cells were pretreated with Noscapine or Doxorubicin or combination and combination index values were calculated using isobolographic method. Apoptosis was assessed by TUNEL staining. Female athymic Nu/nu mice were xenografted with MDA-MB-231 cells and the efficacy of Noscapine, Doxorubicin and combination was determined. Protein expression, immunohistochemical staining were evaluated in harvested tumor tissues. Results: Noscapine inhibited growth of MDA-MB-231 and MDA-MB-468 cells with the IC50 values of 36.16 63.76 and 42.7 64.3 mM respectively. The CI values (,0.59) were suggestive of strong synergistic interaction between Noscapine and Doxorubicin and combination treatment showed significant increase in apoptotic cells. Noscapine showed dose dependent reduction in the tumor volumes at a dose of 150–550 mg/kg/day compared to controls. Noscapine (300 mg/kg), Doxorubicin (1.5 mg/kg) and combination treatment reduced tumor volume by 39.465.8, 34.265.7 and 82.964.5 percent respectively and showed decreased expression of NF-KB pathway proteins, VEGF, cell survival, and increased expression of apoptotic and growth inh