DIM represents a new class of relatively non-toxic antitumorigenic AhR modulators which are of phytochemical origin. Compared to TCDD, DIM is a weak agonist of AhR for induction of CYP1A1 gene expression [20] and activities HDAC inhibitor [21], and it shows abilities to compete for binding of TCDD to the AhR [22]. To test wether the AhR signal pathway could

be activited by DIM in gastric cancer cells, we treated gastric cancer cell line SGC7901 with DIM. Results showed that AhR protein in the total cell lysates gradually decreased (Figure 4C and D), Similar phenomena have been reported by our labs and several other groups [9, 23], the down-regulation of AhR following ligand binding is regarded as an imprtant step of AhR signal pathway [23].

CYP1A1, a classic target gene of AhR, was chosen as an indicator of AhR signal pathway activation. Baseline levels of CYP1A1 expression were not observed in SGC7901 cells in the present study. However, expression of CYP1A1 was significantly increased in a concentration- and time-dependent manner after DIM treatment, indicating the activation of AhR. To confirm the activation of the AhR signal pathway by DIM, we treated SGC7901 cells with a specific AhR antagonist, Selonsertib cost resveratrol. Our results showed that DIM -induced CYP1A1 expression was partially reversed by resveratrol in a concentration-dependent manner. The incomplete reversal of CYP1A1 expression by resveratrol may be due to the fact that AhR is Interleukin-2 receptor not the only regulator of

CYP1A1 transcription [24]. Taken together, these results suggest that DIM could activate the AhR signal pathway in gastric cancer cells. MTT assay demonstrated that the viability of SGC7901 cells was significantly decreased in a concentration- and time-dependent manner after DIM treatment. To further clarify wether this effects was AhR- dependent, we treated SGC7901 cells with DIM and resveratrol, we found that the inhibition effects of DIM on SGC7901 cells growth was partially but not completely reserved by reservatrol, suggesting that DIM inhibits gastric cancer cell growth partially via AhR pathway. This result is in accordance with previous studies: Hong,C found that DIM inhibited growth of both Ah-responsive and Ah-non-responsive breast cancer cells. some of the anti-carcinogenic activities of DIM are AhR –independent [25]. Interestingly, the reversal effect on cell GDC-0941 price proliferation was observed after cells were treated with DIM plus reservatrol for 6 h or 12 h, but not at longer time points (24 h, 48 h and 72 h), this maybe related to the time-effectiveness of reservatrol.