3.2 TA inhibits the proliferation and growth of pancreatic cancer cells
We subsequently examined whether the structural analogues of TA affected the proliferation of pancreatic cancer cells (PANC-1, BxPC-3, and Capan-2). Using the MTS assay, we confirmed that the structural analogues of TA displayed differential inhibitory effects on the cell proliferation of pancreatic cancer (Figure 2b). Among these compounds, TA showed the strongest anti-proliferation activity against pancreatic cancer cells. The preliminary structure-activity relationship of these compounds showed that the position of the side chain attached onansa ring played an important role in the anticancer activity, and the existence of a cyclohexyl group significantly improved the activity. We further confirmed that TA also strikingly inhibited the proliferation of several pancreatic cancer cell lines including CFPAC-1, AsPC-1, MIA PaCa-2, HPAC and SW1990 (Figure 2c). Unexpectedly, TA exhibited stronger proliferation suppressive activity against PANC-1 cells than other pancreatic cancer cell lines. Based on these results, the PANC-1 cells were selected for subsequent experiments. The effect of TA on the growth of PANC-1 cells was evaluated using the colony formation assay. As shown in Figure 2d, TA significantly inhibited the colony formation of PANC-1 cells compared with the control in a concentration-dependent manner.
Additionally, the cell proliferation inhibitory activity of TA was better than that of BP-1-102, a specific STAT3 inhibitor, in pancreatic cancer (Figure S2a). In addition, we also examined whether TA restrained the proliferation of other cancer cells and normal cell lines. Interestingly, TA also strongly inhibited the proliferation of prostate and breast cancer cells rather than normal cell lines (Figure S2b). TA also significantly inhibited the colony formation of other pancreatic cancer cells compared with their control counterparts in a concentration-dependent way (Figure S3). These results indicated that TA exerted a strong inhibitory effect on the proliferation and growth of pancreatic cancer cells by inhibiting the STAT3 signaling pathway.