Curcumin inhibited SHI-1 cell proliferation by arresting the cells in the S-phase, increasing the number of Annexin V-FITC + /PI À cells and promoting the loss of 4W m . The results of PCR and Western blotting showed that curcumin increased the FasL mRNA level; inhibited Bcl-2, NF-jB, and ERK expression; and activated P38 MAPK, JNK, and caspase-3. Additionally, curcumin partially suppressed SHI-1 cell invasion and attenuated the mRNA transcription and secretion of MMP-2 and MMP-9. Discussion and conclusion: This study demonstrates that curcumin not only induces SHI-1 cell apoptosis, possibly via both intrinsic and extrinsic pathways triggered by JNK, P38 MAPK and ERK signaling, but also partially suppresses SHI-1 cell invasion, likely by reducing the levels of transcription and secretion of MMP-2 and MMP-9. KeywordsAntitumor, matrix metalloproteinase, mitogen-activated protein kinase History

OBJECTIVETo investigate the expression of thymidylate synthase (TS), a key enzyme in DNA synthesis that is over‐expressed in several cancer cells, in bladder cancer and its association with patient prognosis and the response to adjuvant therapy.PATIENTS AND METHODSIn all, 67 bladder tissue specimens were obtained from patients who had undergone transurethral resection (TUR). TS expression in bladder cancer and normal bladder tissue was analysed by immunohistochemistry.RESULTSOf the 67 bladder tissue specimens, 47 (70%) and 10 (15%) had positive expression for TS in cancer and normal tissues, respectively. TS expression was greater in patients with Grade 3 (16/17, 94%) than in Grade 1 and 2 (31/50, 64%; P = 0.002). It was also greater in Stage T1 (14/14) than in Stage Ta (33/53, 62%; P = 0.001). Furthermore, patients with negative TS expression had a longer postoperative recurrence‐free survival (RFS) than those with positive expression during the 5 year follow‐up (P = 0.028). In the patients with positive TS‐expressing tumours, adjuvant therapy significantly improved RFS (P < 0.001).CONCLUSIONSHigh TS expression might be a marker of poor prognosis for patients with bladder cancer. In addition, patients with high TS expression might also be benefit from adjuvant therapy.

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