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.