Spontaneous Tumor Regression in a Syngeneic Rat Model of Liver Cancer: Implications for Survival Studies

Abstract

Purpose: To characterize tumor growth of NISI cells implanted into the liver of Sprague-Dawley rats to determine if this model could be used for survival studies. These results were compared with tumor growth after implantation with MeA-RH7777 cells. Materials and Methods: NISI or McA-RH7777 cells were implanted into the liver of Sprague-Dawley rats (n = 20 and n = 12, respectively) using ultrasound (US) guidance, and tumor growth was followed by using US. Serum profiles of 19 cytokines were compared in naive versus tumor-bearing rats. Results: Both types of tumors were visible on US 1 week after tumor implantation, but the mean tumor volume of NISI tumors was larger compared to MeA-RH7777 tumors (231 mm(3) vs 82.3 mm(3), respectively). Tumor volumes in both groups continued to increase, reaching means of 289 mm(3) and 160 mm(3) in NISI and McA-RH7777 groups, respectively, 2 weeks after tumor implantation. By week 3, tumor volumes had decreased considerably, and six tumors (50%) in the McA-RH7777 had spontaneously regressed, versus two (10%) in the NISI group. Tumor volumes continued to decrease over the following 3 weeks, and complete tumor regression of all tumors was seen 5 weeks and 6 weeks after tumor implantation in the MeA-RH7777 and NISI groups, respectively. In an N1S1-implanted rat, multiple cytokines that have been shown to correlate with the ability of the tumor to survive in a hostile environment were increased by as much as 50%, whereas the average increase in cytokine levels was 90%. These findings suggest that the net cytokine environment favors an antitumor immune response. A similar trend was observed in a rat with a McA-RH7777 tumor, and the increase in cytokine levels was considerably more pronounced, with an average increase of 320%. Conclusions: The model of NISI cell implantation in the liver of Sprague Dawley rats is not ideal for survival studies and should only be used with great caution in short-term studies that involve cancer therapies.