Abstract: Objective：To preliminarily verify the cross talk between tissue factor/active coagulation factor Ⅶ (TF/FⅦa) and epidermal growth factor receptor (EGFR) pathways in human colon cancer cells in culture. Methods: FⅦa was treated to HT-29 (KRAS-wild type) and LoVo (KRAS-mutant) colon cancer cells to activate TF/FⅦa pathway, qRT-PCR and Western blot were used to detect the expressions of amphiregulin (AREG) and epiregulin (EREG), ligands of EGFR on mRNA and protein levels, respectively. After knocking down expression of TF by TF-targeted siRNA transfection, FⅦa was treated and mRNA expressions of AREG and EREG were detected to see whether the FⅦa-induced effects were dependent on TF. Expressions of mRNA of TF and FⅦ were detected by qRT-PCR following the activation of EGFR pathway by treatment with epidermal growth factor (EGF) to HT-29 and LoVo cells. Results: After TF/FⅦa pathway was activated, for HT-29 cells, expressions of AREG (on mRNA level) and EREG (both on mRNA and protein level) were significantly down-regulated versus those of control group, gene expressions of AREG and EREG were 0.55±0.09 vs.0.99±0.09, 0.67±0.10 vs.1.02±0.02, protein expressions of EREG were 0.54±0.09 vs.1.04±0.13, all P＜0.05. For LoVo cells, expressions of AREG (both on mRNA and protein level) and EREG (on protein level) were significantly up-regulated versus those of control group, gene expression of AREG were 1.87±0.39 vs. 0.93±0.23, protein expressions of AREG and EREG were 3.09±0.73 vs.1.11±0.21, 1.53±0.19 vs.0.97±0.23, all P＜0.05. The regulating effect of AREG and EREG mRNA expression by FⅦa in HT-29 and LoVo cells could both be partly blocked by knocking down TF expression. For HT-29 cells, activation of EGFR pathway induced no significant TF mRNA expression, FⅦ mRNA expression was not detected. However，for LoVo cells, activation of EGFR pathway induced significantly higher mRNA expressions of both TF and FⅦ, expressions were 1.53±0.23 vs.1.00±0.23, 53.20±6.08 vs.1.00±0.15, all P＜0.05. Conclusion: In colon cancer cell LoVo, when activated, TF/FⅦa pathway and EGFR pathway could interact through upregulating the other pathway’s effectors, and mutant KRAS might play a critical role in the two pathways’cross talk.

Key words: Colonic neoplasms, Thromboplastin, Factor Ⅶa, Receptor, epidermal growth factor