The effects of Nimesulide combined with cisplatin on lung cancer

Abstract

To study the effects of cyclooxygenase 2 selective inhibitor Nimesulide (NIM) combined with Cisplatin (DDP) on human lung cancer and the possible mechanisms, the proliferation and appoptosis of human lung cancer cell line A549 were evaluated by MTT reduction assay and flow cytometry respectively. The inhibitory effect on neoplasiain vivo was tested on nude mice subcutaneously implanted tumor. Our results showed that NIM and DDP could inhibit A549 cell proliferation in a concentration-dependent pattern; this action was enhanced when NIM (25 μmol/L) was given in combination with DDP and they worked in a synergistic or additive pattern as DDP concentration ≥1 μg/ml. NIM and DDP could induce A549 cells apoptosis and the action was augmented when used in combination (P<0.01). NIM and DDP could inhibit the growth of subcutaneously implanted tumors on nude mice (P<0.05,P<0.01) and the inhibitory rate of NIM combined with DDP was significantly higher than that of NIM or DDP group (P<0.01,P<0.01). It is concluded that combined use of NIM and DDP has significant synergistic antitumor effects on lung cancer cell line A549 and in animalsin vivo. The synergy may be achieved by growth inhibition and apoptosis induction.

Keywords

lung cancer / apoptosis / cyclooxygenase 2 / cisplatin

References

[1] YaoM, KargmanS, LamE C, et al. . Inhibition of cyclooxygenase-2 by rofecoxib attenuates the growth and metastatic potential of colorectal carcinoma in mice. Cancer Res, 2003, 63(3): 586-586

[2] ChengA S, ChanH L, LeungW K, et al. . Specific COX-2 inhibitor, NS-398, suppresses cellular proliferation and induces apoptosis in human hepatocellular carcinoma cells. Int J Oncol, 2003, 23(1): 113-113

[3] LiJ Y, WangX Z, ChenF L, et al. . Nimesulide inhibits proliferation via induction of apoptosis and cell cycle arrest in human gastric adenocarcinoma cell line. World J Gastroenterol, 2003, 9(5): 915-915

[4] MilasL, MasonK A, CraneC H, et al. . Improvement of radiotherapy or chemoradiotherapy by targeting COX-2 enzyme. Oncology (Huntingt), 2003, 17(5 Suppl 5): 15-15

[5] WuY D, ChenY, ChenW J, et al. . Effects of use of rh-IFN-γ on the anti-proliferative capacity on HL-60 cells caused by curcumin. Ai Zheng (Chinese), 1999, 18(6): 635-635

[6] HanR. Chemoprophylaxis and Drug treatment on Tumor, 19911st editionBeijing, Union Publishing Company of Beijing Medical University and China Union Medical University: 419-420

[7] FangH Y, LinT S, LinJ P, et al. . Cyclooxygenase-2 in human non-small cell lung cancer. Eur J Surg Oncol, 2003, 29(2): 171-171

[8] Sanchez-AlcazarJ A, BradburyD A, PangL, et al. . Cyclooxygenase (COX) inhibitors induce apoptosis in nonsmall cell lung cancer through cyclooxygenase independent pathways. Lung Cancer, 2003, 40(1): 33-33

[9] MizutaniY, KamoiK, UkimuraO, et al. . Synergistic cytotoxicity and apoptosis of JTE-522, a selective cyclooxygenase-2 inhibitor, and 5-fluorouracil against bladder cancer. J Urol, 2002, 168(6): 2650-2650

[10] BecerraC R, FrenkelE P, AshfaqR, et al. . Increased toxicity and lack of efficacy of Rofecoxib in combination with chemotherapy for treatment of metastatic colorectal cancer: A phase II study. Int J Cancer, 2003, 105(6): 868-868