A Model of Combination Therapy of Lewis Lung Carcinoma using Resection and Cytostatics

We propose a model of combination treatment of Lewis lung carcinoma (LLC) in C57BL/6 mice that includes tumor resection and chemotherapy. A single injection of 5×106 LLC cells into the right lateral subcostal region caused the growth of the primary tumor and its metastasis to the lung. For reducing metastasis and mortality after resection, the primary tumor should be removed with subcutaneous fat on day 8 after inoculation. Antitumor and antimetastatic effects and reduced mortality were achieved by intraperitoneal injection of carboplatin (63.3 mg/kg) and paclitaxel (13.3 mg/kg); chemotherapy was administered twice. The combination of the two approaches increased the survival: the antitumor and antimetastatic effects were observed in 60% of mice with LLC relative to resection alone or treatment with cytostatics alone. However, chemoresistance was formed in 40% of mice, the values of the tumor growth inhibition index and the metastasis inhibition index decreased. This was accompanied by the appearance of cancer stem cells in the circulation with the potential for the formation of spheroids in vitro. The presented model (combination of tumor resection and chemotherapy) can be used in the development of new approaches to improve treatment efficiency in patients with lung cancer.