**3. Conclusion**

In this review we aimed to focuse on the explanation the role of inflammation on the ABCG2 expression and function, using MCF-7 human breast carcinoma cell line. Proinflammatory cytokines have been found to be present within the micro-environment of tumors and inflammation. They are able to modulate the expression and function of different drug transporters. Mosaffa et al. showed that that proinflammatory cytokines IL-1β and TNF-α induce ABCG2 mRNA and protein expression and increase its function in MCF-7 cells. In MCF-7/MX, these cytokines increased ABCG2 protein expression and function, but they have no influence on the transporter mRNA levels.

Cyclooxygenase-2 (COX-2) is induced by mitogenic and inflammatory stimuli such as growth factors and cytokines, which results in enhanced synthesis of PGs in neoplastic and inflamed tissues. Kalalinia et al. studies had aimed to explore the potential link between COX-2 expression and development of multidrug resistance phenotype in MCF-7 cell line. They reported that COX-2 inducer TPA (12-O-tetradecanoylphorbol-13-acetate) caused a considerable increase up to 9-fold in ABCG2 mRNA expression in parental MCF-7 cells, while a slight increase in ABCG2 expression was observed in the resistant cell line MCF-7/MX. They also showed a positive corrolation between ABCG2 protein expression and COX-2 protein level in each cell line. On the other hand, celecoxib (a selective inhibitor of COX-2) up-regulated the expression of ABCG2 mRNA in MCF-7 and MCF-7/MX cells, which was accompanied by increased ABCG2 protein expression. Furthermore, TPA could increase ABCG2 function in all cell lines with the greatest stimulatory effects in MCF-7/MX (more than 6 times the control level). In addition, celecoxib inverted the effects of TPA on ABCG2 function. This effect was more obvious in MCF-7/MX.

Several studies have demonstrated that anti-inflammatory drugs like NSAIDs and some glucocorticoids could be effective in chemosensitizing of the many carcinoma cell lines to cytotoxic agents. The pharmacological modulation of ABCG2 in MCF-7 cells by dexamethasone and indomethacin was investigated by elahian et al. . They showed that dexamethasone induced downregulation of ABCG2 mRNA compared to controls in both MCF-7 and MCF-7/MX cell lines, whereas no changes were noted in the presence of indomethacin. The level of ABCG2 protein was decreased in dexamethasone treated MCF-7/MX cells. Cotreatment of mitoxantrone with different concentrations of dexamethasone and indomethacin sensitized parental and resistant MCF-7 cells to mitoxantrone cytotoxicity. Dexamethasone also increased the accumulation of mitoxantrone in the MCF-7/MX cell line, indicating an inhibitiory effect on the ABCG2 protein.

In this review, we describe the effects of proinflammatory cytokines (IL-1β and TNF-α), inflammatory mediator (COX-2) and anti-inflammatory drugs (celecoxib and dexametashone) on the expression of ABCG2 which addressed concerning to finding a new adjutant therapy for patients with cancer experiencing resistance to cancer treatment.
