Imageable orthothopic metastatic mouse models for the identification of the antitumor and antimetastatic efficacy of traditional Chinese medicine (TCM).

Abstract

e14700 Background: Traditional Chinese Medicine (TCM) is still poorly understood with regard to the types of cancer it is effective against, as well as its mechanism of action. Modernization of TCM evaluation is necessary in order for TCM to be effectively developed. We report here on the use of patient-like orthotopic nude-mouse models of metastatic cancer to obtain proof-of-concept that TCM combinations can have anti-tumor and anti-metastatic activity. Methods: In the present study, human and mouse lung cancer and pancreatic cancer cell lines (H460, Lewis lung carcinoma [LLC] and MIA-PaCa-2, respectively), labeled with red fluorescent protein (RFP) or green fluorescent protein (GFP) were used. The cells were initially implanted subcutaneously or injected in the tail vein in nude mice. Subcutaneous tumors were harvested to obtain tissue fragments which were implanted orthotopically in nude mice. These models were used to evaluate the anti-tumor and anti-metastatic efficacy of the TCM termed Fufang LQ (LQ), which contains a mixture of Chinese herbs. Results: LQ (gavage, 600 mg/kg/day) significantly inhibited pancreatic and lung cancer tumor growth as measured by imaging, tumor and weight in both subcutaneous and orthotopic models. LQ was significantly efficacious against primary and metastatic cancer in the above models without weight loss in contrast to drugs such as doxorubicin and cisplatin, which caused significant weight loss. Survival of tumor-bearing mice was also prolonged by LQ treatment. Conclusions: The results of the present study indicate that TCM can have non-toxic efficacy, in contrast to standard chemotherapy drugys, against metastatic pancreatic and lung cancer in clinically-relevant orthotopic mouse models of cancer, an important step toward the clinical development of TCM.