DOI QR코드

DOI QR Code

Synergistic Anti-tumor Effect of KLF4 and Curcumin in Human Gastric Carcinoma Cell Line

  • Ji, Jun (Department of Central Laboratory, Dalian Municipal Central Hospital) ;
  • Wang, He-Shuang (Department of Central Laboratory, Dalian Municipal Central Hospital) ;
  • Gao, Yan-Yan (Department of Central Laboratory, Dalian Municipal Central Hospital) ;
  • Sang, Li-Min (Department of Central Laboratory, Dalian Municipal Central Hospital) ;
  • Zhang, Li (Department of Central Laboratory, Dalian Municipal Central Hospital)
  • Published : 2014.10.11

Abstract

Kr$\ddot{u}$ppel-like factor 4 is a transcription factor which plays an important role in development and progression of various carcinomas. Curcumin characterized by excellent anti-cancer properties is regarded as a serviceable natural compound used in carcinoma therapy. This study aimed at exploring the impact of KLF4 overexpression in cooperation with curcumin on the proliferation, apoptosis and invasion of human gastric carcinoma BGC-823 cells. Flow cytometry analysis, CCK-8 assays, transwell assays and Western blot results showed that KLF4 overexpression combined with curcumin had significant anti-proliferation, pro-apoptosis and anti-invasion effects on BGC-823 cells. We also found that KLF4 had synergistic effects with curcumin, better promoting apoptosis and inhibiting proliferation and invasion of gastric carcinona cells. These results indicate that KLF4 could be used as a potential therapeutic target; curcumin could act as an auxiliary and provide a promising therapeutic strategy in stomach cancer.

Keywords

References

  1. Bloch O, Amit-vazina M, Yona E, et al (2014). Increased ERK and JNK activation and decreased ERK/JNK ratio are associated with long-term organ damage in patients with systemic lupus erythematosus. Rheumatology, 53 (6), 1034-42. https://doi.org/10.1093/rheumatology/ket482
  2. Ekinci AS, Bal O, Ozatli T, et al (2014). Gastric carcinoma with bone marrow metastasis: a case series. J Gastric Cancer, 14, 54-7. https://doi.org/10.5230/jgc.2014.14.1.54
  3. Feng J, Tao T, Yan W, Chen CS, Qin X (2014). Curcumin inhibits mitochondrial injury and apoptosis from the early stage in EAE mice. Oxid Med Cell Longev, 2014, 728751.
  4. Flandez M, Guilmeau S, Blache P, Augenlicht LH (2008). KLF4 regulation in intestinal epithelial cell maturation. Experimental Cell Res, 314, 3712-23. https://doi.org/10.1016/j.yexcr.2008.10.004
  5. Gryko M, Guzinska-ustymowicz K, Kisl UK J, et al (2014). High Fas expression in gastric carcinoma cells as a factor correlating with the occurrence of metastases to regional lymph nodes. Adv Med Sci, 59, 47-51. https://doi.org/10.1016/j.advms.2013.07.005
  6. Hinoi E, Iezaki T, Fujita H, et al (2014). PI3K/Akt is involved in brown adipogenesis mediated by growth differentiation factor-5 in association with activation of the Smad pathway. Biochem Biophys Res Commun, 450, 255-60. https://doi.org/10.1016/j.bbrc.2014.05.108
  7. Huang G, Dang ZF, Dang YM, et al (2014). Expression and underlying roles of IGFBP-3 in paclitaxel-treated gastric cancer Sgc-7901 cells. Asian Pac J Cancer Prev, 15, 5741-5. https://doi.org/10.7314/APJCP.2014.15.14.5741
  8. Kim SJ, Yoo KY, Jeong CW, et al (2009). Urinary trypsin inhibitors afford cardioprotective effects through activation of PI3K-Akt and ERK signal transduction and inhibition of p38 MAPK and JNK. Cardiology, 114, 264-70. https://doi.org/10.1159/000234321
  9. Li Z, Lu H, Li ZB (2014). The PI3K/Akt signalling pathway may play an internal role related to abnormal condylar growth: a preliminary study. Int J Oral Maxillofac Surg, [Epub ahead of print].
  10. Lu Y, Wei C, Xi Z (2014). Curcumin suppresses proliferation and invasion in non-small cell lung cancer by modulation of MTA1-mediated Wnt/beta-catenin pathway. In Vitro Cell Dev Biol Anim, [Epub ahead of print].
  11. Lubkov V, Bar-sagi D (2014). E-cadherin-mediated cell coupling is required for apoptotic cell extrusion. Curr Biol, 24, 868-74. https://doi.org/10.1016/j.cub.2014.02.057
  12. Mccain J (2013). The MAPK (ERK) pathway: investigational combinations for the treatment of BRAF-mutated metastatic melanoma. P T, 38 (2), 96-108.
  13. Mehta HJ, Patel V, Sadikot RT (2014). Curcumin and lung cancer-a review. Target Oncol, [Epub ahead of print].
  14. Meng FM, Yang JB, Yang CH, et al (2012). Vitexicarpin induces apoptosis in human prostate carcinoma PC-3 cells through G2/M phase arrest. Asian Pac J Cancer Prev, 13, 6369-74. https://doi.org/10.7314/APJCP.2012.13.12.6369
  15. Pamies P (2014). E-cadherin-guided migration. Nat Mater, 13, 664.
  16. Pryczynicz A, Gryko M, Niewiarowska K, et al (2014). Bax protein may influence the invasion of colorectal cancer. World J Gastroenterol, 20, 1305-10. https://doi.org/10.3748/wjg.v20.i5.1305
  17. Rusyn EV, Reynolds ER, Shao H, et al (2000). Rit, a non-lipidmodified Ras-related protein, transforms NIH3T3 cells without activating the ERK, JNK, p38 MAPK or PI3K/Akt pathways. Oncogene, 19, 4685-94. https://doi.org/10.1038/sj.onc.1203836
  18. Theron KE, Penny CB, Hosie MJ (2013). The Bax/Bcl-2 apoptotic pathway is not responsible for the increase in apoptosis in the RU486-treated rat uterus during early pregnancy. Reprod Biol, 13, 290-7. https://doi.org/10.1016/j.repbio.2013.09.002
  19. Tiwari N, Meyer-schaller N, Arnold P, et al (2013). Correction: Klf4 is a transcriptional regulator of genes critical for EMT, including Jnk1. PLoS One, 8 (2), e57329.
  20. Wang Z, Jiang C, Ganther H, Lu J (2001). Antimitogenic and proapoptotic activities of methylseleninic acid in vascular endothelial cells and associated effects on PI3K-AKT, ERK, JNK and p38 MAPK signaling. Cancer Res, 61, 7171-8.
  21. Wei D, Gong W, Kanai M, et al (2005). Drastic down-regulation of Kruppel-like factor 4 expression is critical in human gastric cancer development and progression. Cancer Res, 65, 2746-54. https://doi.org/10.1158/0008-5472.CAN-04-3619
  22. Xu XB, Chen B, Liu WY (2014). Curcumin inhibits the invasion of thyroid cancer cells via down-regulation of PI3K/Akt signaling pathway. Gene, 546, 226-32. https://doi.org/10.1016/j.gene.2014.06.006
  23. Xue X, Yu JL, Sun DQ, et al (2014). Curcumin induces apoptosis in SGC-7901 gastric adenocarcinoma cells via regulation of mitochondrial signaling pathways. Asian Pac J Cancer Prev, 15, 3987-92. https://doi.org/10.7314/APJCP.2014.15.9.3987
  24. Yoon HS, Ghaleb AM, Nandan MO, et al (2005). Kruppellike factor 4 prevents centrosome amplification following gamma-irradiation-induced DNA damage. Oncogene, 24, 4017-25. https://doi.org/10.1038/sj.onc.1208576
  25. You H, Lei P, Andreadis ST (2013). JNK is a novel regulator of intercellular adhesion. Tissue Barriers, 1, 268-45.
  26. Zang S, Liu T, Shi J, Qiao L (2014). Curcumin: a promising agent targeting cancer stem cells. Anticancer Agents Med Chem, 14, 787-92. https://doi.org/10.2174/1871520614666140521114735
  27. Zhang N, Zhang J, Shual L, et al (2012). Kruppel-like factor 4 negatively regulates beta-catenin expression and inhibits the proliferation, invasion and metastasis of gastric cancer. Int J Oncol, 40, 2038-48.

Cited by

  1. Synergistic effect of HMGB1 knockdown and cordycepin in the K562 human chronic myeloid leukemia cell line vol.12, pp.3, 2015, https://doi.org/10.3892/mmr.2015.3928
  2. Spices for Prevention and Treatment of Cancers vol.8, pp.8, 2016, https://doi.org/10.3390/nu8080495
  3. Product Development Studies on Sonocrystallized Curcumin for the Treatment of Gastric Cancer vol.7, pp.2, 2015, https://doi.org/10.3390/pharmaceutics7020043