Based on the fact that (1) metformin is able to inhibit COX2 [60]; (2) PGE2, a product catalyzed by COX2, is capable of promoting stem cell expansion [61] and mobilization [62]; and (3) blocking PGE2 abrogates bladder cancer chemo-resistance by repressing CK14+ cells repopulation [62], we explored the possibility of metformin effect on COX2/PGE2 pathway and found that metformin is indeed capable of downregulating COX2 and subsequently reducing the level of PGE2. The gene discussed is PTGS2; the disease is urinary bladder cancer.