Abstract��OBJECTIVE To explore effection and significance of sunitinib on gefitinib resistance of lung cancer cells. METHODS Cell proliferation inhibition of 28 gefitinib resistance lung cancer patients tumor tissues extracted with sunitinib treatment were measured using MTT assay. After sunitinib treatment, sensitivity of gefitinib resistance cells were measured by CellTiter-Glo method;The accumulation of Rh-123 in gefitinib resistant cells with sunitinib treatment were measured by FCM method. Accumulation of multi-drug resistance protein (MDR),transcription factors ��B(NF-��B)and vascular endothelial growth factor(VEGF) were examined using Western blotting after sunitinib treatment on gefitinib resistance cells. RESULTS Cell proliferation were inhibited by dose dependent after sunitinib treatment, IC50 is (6.73��1.57) ��mol��L-1. Sensitivity of gefitinib resistance cells were significantly increased ,and decreased the IC50 of gefitinib for inhibiting resistance cells after 1 and 2 ��mol��L-1 sunitinib combine with gefitinib treatment, IC50 of gefitinib is (38.64��1.29) and (20.37��1.75) ��mol��L-1 respectively. The accumulation of Rh-123 in gefitinib resistant cells with 1 ��mol��L-1 sunitinib treatment were significantly increased(P<0.05),fluorescent density increased by 2.44 times following treatment with 1 ��mol��L-1 of sunitinib, accumulation of Rh-123 in gefitinib resistant cells with 2 ��mol��L-1 sunitinib treatment is larger significantly increased(P<0.01), fluorescent density increased by 5.64 times following treatment with 2 ��mol��L-1 of sunitinib; expression level of MDR��NF-��B and VEGF proteins were significantly reduced after 1 and 2 ��mol��L-1 sunitinib treatment. CONCLUSION Sunitinib is able to reverse the gefitinib resistance, the theoretical foundation is provided for clinical treatment of patients with gefitinib resistance.
DEARING K R, SANGAL A, WEISS G J. Maintaining clarity:review of maintenance therapy in non-small cell lung cancer[J]. World J Clin Oncol, 2014,5(2):103-113.
[2]
ASAMURA H, CHANSKY K, CROWLEY J, et al. The international association for the study of lung cancer lung cancer staging project:proposals for the revision of the N descriptors in the forthcoming 8th edition of the TNM classification for lung cancer [J]. J Thorac Oncol,2015,10(12):1675-1684.
[3]
SHI H, ZHANG X, WANG F,et al. Curative effect analysis of different treatments for gefitinib-resistance advanced non-small cell lung cancer patients[J]. Int J Clin Exp Med, 2015,8(9):16064-16070.
[4]
MELGUIZO C, PRADOS J, LUQUE R, et al. Modulation of multidrug resistance gene expression in peripheral blood mononuclear cells of lung cancer patients and evaluation of their clinical significance[J]. Cancer Chemother Pharmacol, 2013,71(2):537-541.
[5]
HUANG J S, ZHAO M D, SHI J M, et al. Expression of multidrug resistance 1 and multidrug resistance-related protein 1 in C57BL/6 mice treated with benzene[J]. Genet Mol Res, 2013,12(4):5842-5850.
[6]
UGUR H C, TASPINAR M, ILGAZ S, et al. Chemotherapeutic resistance in anaplastic astrocytoma cell lines treated with a temozolomide-lomeguatrib combination[J]. Mol Biol Rep, 2014,41(2):697-703.
[7]
GATOUILLAT G, MAGID A A, BERTIN E, et al. Medicarpin and millepurpan, two flavonoids isolated from Medicago sativa, induce apoptosis and overcome multidrug resistance in leukemia P388 cells[J]. Phytomedicine, 2015,22(13):1186-1194.
[8]
SONG L, LI Y, LI W, et al. miR-495 enhances the sensitivity of non-small cell lung cancer cells to platinum by modulation of copper-transporting P-type adenosine triphosphatase A (ATP7A)[J]. J Cell Biochem, 2014,115(7):1234-1242.
[9]
ANREDDY N, PATEL A, SODANI K, et al. PD173074, a selective FGFR inhibitor, reverses MRP7 (ABCC10)-mediated MDR[J]. Acta Pharm Sin B(ҩѧѧ��Ӣ�İ�), 2014,4(3):202-207.
[10]
TEIJARO C N, MUNAGALA S, ZHAO S, et al. Synthesis and biological evaluation of pentacyclic strychnos alkaloids as selective modulators of the ABCC10 (MRP7) efflux pump[J]. J Med Chem, 2014,57(24):10383-10390.
[11]
LEONARD B, MCCANN J L, STARRETT G J, et al. The PKC/NF-��B signaling pathway induces APOBEC3B expression in multiple human cancers[J]. Cancer Res, 2015,75(21):4538-4547.
[12]
WANG H, WANG X, LI Y, et al. The proteasome inhibitor bortezomib reverses P-glycoprotein-mediated leukemia multi-drug resistance through the NF-kappa B pathway[J]. Pharmazie, 2012 ,67(2):187-192.
[13]
SOROLLA A, YERAMIAN A, VALLS J, et al. Blockade of NF��B activity by sunitinib increases cell death in bortezomib-treated endometrial carcinoma cells[J]. Mol Oncol, 2012,6(5):530-541.
[14]
PAN F, TIAN J, ZHANG X C, et al. Inhibitory effect of sun itinib on EGFR TK1-resistant human non-small cell lung cancer cell line A549 and its mechanism[J]. Chin Pharmacol Bull(�й�ҩ��ѧͨ��), 2011,27(8):1121-1125.
[15]
HU M M, HU Y, LI B L. Research progress of clincal translation on signal pathway and relevant drugs in tumor angiogenesis[J]. Chin J Cancer Biother(�й���������������־), 2014,21(1):86-94.
[16]
GROCHOT-PRZECZEK A, DULAK J, JOZKOWICZ A. Therapeutic angiogenesis for revascularization in peripheral artery disease[J]. Gene, 2013,525(2):220-228.
[17]
HAN K S, RAVEN P A, FREES S, et al. Cellular adaptation to VEGF-targeted antiangiogenic therapy induces evasive resistance by overproduction of alternative endothelial cell growth factors in renal cell carcinoma[J]. Neoplasia, 2015,17(11):805-816.