|
|
PP2 enhances intercellular communication of gap junction in breast cancer Hs578T cells |
DONG Shu-Ying, ZHENG Chao, JIANG Guo-Jun, HAN Xi, TONG Xu-Hui |
Department of Pharmacology,Faculty of Pharmacy,Bengbu Medical College,Bengbu 233000,China |
|
|
Abstract Objective: To investigate the effect of Src kinase inhibitor PP2 on intercellular communication of gap junction in breast cancer cells.
Methods: Cultured breast cancer Hs578T cells were treated with various concentrations of pp2 (0,1,2,4,8,16,32 μmol/L) for 24h.Cell growth was determined by MTT assay; dye spread in Hs578T cells was measured by Parachute assay; and the expression of Src kinase in Hs578T cells was detected by Western blot.
Results: MTT assay showed that the survive rate of Hs578T cells treated with PP2 (1~8 μmol/L) was 98%±3%~94%±4%.Parachute assay showed that compared to control group the standard normalized dye spread rates of Hs578T cells treated with 1,2,4 and 8 μmol/L PP2 were 1.60±0.08,2.00±0.05,2.20±0.05 and 2.70±0.09,respectively (all P<0.01).Moreover,compared to control group at the same time points,the standard normalized dye spread of Hs578T cells treated with 8 μmol/L PP2 for 6,12 and 24 h were 1.4±0.05,1.7±0.06,and 2.2±0.07,respectively (all P<0.01).Western blot showed that the expression ratios of Src kinase/β-actin of Hs578T cells treated with 1,2,4 and 8 μmol/L PP2 for 24 h were 0.93±0.02,0.70±0.09,0.66±0.09 and 0.36±0.10,which were significantly inhibited compared with control group (P<0.05 or 0.01).And the expression ratio of Src kinase/β-actin of Hs578T cells treated with 8 μmol/L PP2 for 6,12 and 24h was 0.82±0.03,0.66±0.08 and 0.59±0.09,which were all inhibited significantly compared to control group (P<0.01).
Conclusion: PP2 enhances the gap junction function in breast cancer Hs578T cells,which is probably related to the inhibition of Src kinase.
|
Received: 17 December 2012
Published: 25 September 2013
|
|
PP2可增强乳腺癌Hs578T细胞缝隙连接功能
目的:探讨Src激酶抑制剂PP2对乳腺癌细胞Hs578T缝隙连接功能的影响。
方法:MTT法检测PP2对乳腺癌细胞生长的影响;细胞接种荧光示踪法观察PP2对乳腺癌细胞之间荧光传递功能的影响;Western blot法检测PP2对乳腺癌细胞Src激酶表达的影响。
结果:1~8 μmol/L浓度的PP2对乳腺癌细胞生长几乎无影响;细胞接种荧光示踪结果显示,1~8 μmol/L的PP2能显著增强细胞荧光传递功能(P<0.01),8 μmol/L的PP2作用6、12和24 h后细胞荧光传递功能亦明显增强(P<0.01);Western blot结果显示,PP2(1~8 μmol/L)可显著降低Src激酶表达(P<0.05~0.01),8 μmol/L PP2作用6、12和24 h后Src激酶的表达亦明显降低(P<0.01)。
结论:PP2能增强乳腺癌细胞Hs578T的缝隙连接功能,这种增强作用可能与其降低Src激酶表达有关。
关键词:
乳腺肿瘤,
src族激酶类/拮抗剂和抑制剂,
连接蛋白类,
肿瘤细胞, 培养的
|
|
[[1]] |
WILLECKE K,EIBERGER J,DEGEN J,et al.Structural and functional diversity of connexin genes in the mouse and human genome
|
|
|
[[J]] |
Biol Chem,2002,383(5):725-737.
|
|
|
[[2]] |
TONG Xuhui,DONG Shuying,JIANG Guojun,et al(童旭辉,董淑英,蒋国君,等). Influence of Cx26/Cx32 gap junction channel on antineoplastic effect of etoposide in Hela cells
|
|
|
[[J]] |
Journal of Southern Medical University(南方医科大学学报),2012,32(3):329-332.(in Chinese)
|
|
|
[[3]] |
JIANG Guojun,TONG Xuhui,ZHU Xiaoguang,et al(蒋国君,童旭辉,祝晓光,等).Influence of expression of Cx43 in breast cancer cells Hs578T on the cytotoxicity of adriamycin
|
|
|
[[J]] |
Chinese Pharmacological bulletin(中国药理学通报),2012,28(5):641-647.(in Chinese)
|
|
|
[[4]] |
SUMMY J M,GALLICK G E.Src family kinases in tunor progression and metastasis
|
|
|
[[J]] |
Cancer Metastusis Rev,2003,22(4):337-358.
|
|
|
[[5]] |
SHEN Y,KHUSIAL P R,LI X,et al.SRC utilizes Cas to block gap junctional communication mediated by connexin43
|
|
|
[[J]] |
J Biol Chem,2007,282(26):18914-18921.
|
|
|
[[6]] |
SELTANA A,GUEZGUEA A,LEPAGE M,et al.Src family kinase inhibitor PP2 accelerates differentiation in human intestinal epithelial cells
|
|
|
[[J]] |
Biochem Biophys Res Commun, 2013,430:1195-1200.
|
|
|
[[7]] |
SOLAN J L,LAMPE P D.Connexin phosphorylation as a regulatory event linked to gap junction channel assembly
|
|
|
[[J]] |
Biochim Biophys Acta,2005,1711(2):154-163.
|
|
|
[[8]] |
PAHUJAA M,ANIKIN M,GOLDBERG G S.Phosphorylation of connexin43 induced by Src:Regulation of gap junctional communication between transformed cells
|
|
|
[[J]] |
Experimental Cell Research,2007,313(20):4083-4090.
|
|
|
[[9]] |
HE B,TONG X H,WANG L Z,et al.Tramadol and flurbiprofen depress the cytotoxicity of cisplatin via their effects on gap junctions
|
|
|
[[J]] |
Clin Cancer Res,2009,15(18):5803-5810.
|
|
|
[[10]] |
HUANG R P,HOSSAIN M Z,HUANG R,et al.Connexin 43 (cx43) enhances chemotherapy-induced apoptosis in human glioblastoma cells.
|
|
|
[[J]] |
Int J Cancer,2001,92(1):130-138.
|
|
|
[[11]] |
KASHIWAGI K,VIRGONA N,YAMADA J,et al.Bowman-Birk protease inhibitor from soybeans enhances cisplatin-induced cytotoxicity in human mesothelioma cells
|
|
|
|
Viewed |
|
|
|
Full text
|
|
|
|
|
Abstract
|
|
|
|
|
Cited |
|
|
|
|
|
Shared |
|
|
|
|
|
Discussed |
|
|
|
|