3.4 TA inhibits pancreatic tumor growth in vivo
Since we observed the inhibition of proliferation and growth of pancreatic cancer cells after treatment with TA, we next sought to identify whether it would apparently repress pancreatic cancer xenograft tumor growth. We tested this hypothesis using a subcutaneous xenograft model of PANC-1 cells in nude mice. The tumor-bearing nude mice were randomly divided into five groups: negative control group, positive control group, low-dose group, medium-dose group, and high-dose group. Gemcitabine hydrochloride, approved by the US Food and Drug Administration (FDA) as a first-line agent for the treatment of pancreatic cancer, was used as a positive control. The dosages of TA for the animal experiment were set at 10 mg/kg/d, 20 mg/kg/d, and 40 mg/kg/d based on our experience and pharmacological knowledge. As expected, intraperitoneal injection of TA dose-dependently caused significant inhibition of pancreatic tumor growth in the xenograft model. The inhibition of pancreatic tumor growth in the medium-dose group was as same as the positive control group (Figure 4a). As exhibited in Figure 4b,c, the tumor volume and tumor weight were significantly reduced in the TA-treated groups compared with the negative control group. H&E staining of tumor tissue sections showed distinct tumor cell necrosis and immunohistological analysis indicated prominent reduction in the expression of proliferating cell nuclear antigen (PCNA) and Ki-67 within the tumor tissues of the TA-treated groups compared with tissues from the negative control group (Figure 4d). Importantly, there was no significant difference in body weight of mice among each group, indicating that TA had no apparent toxicity (Figure 4e). Furthermore, the pathological changes in the main organs of mice were also inspected by H&E staining, and there was no significant toxicity at the effective dose (Figure 4f). In a word, TA markedly retarded tumor growth in vivo by inhibiting the proliferative capacity of PANC-1 cells, and had no obvious toxicity and side effects.