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Article

TLR4 induces tumor growth and inhibits paclitaxel activity in MyD88‑positive human ovarian carcinoma in vitro

  • Authors:
    • An‑Cong Wang
    • Yue‑Bing Ma
    • Feng‑Xia Wu
    • Zhi‑Fang Ma
    • Nai‑Fu Liu
    • Rong Gao
    • Yong‑Sheng Gao
    • Xiu‑Gui Sheng
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, Linyi People's Hospital, Linyi, Shandong 276002, P.R. China, Department of Gynecologic Oncology, Shandong Cancer Hospital and Institute, Jinan, Shandong 250117, P.R. China, Department of Anatomy, Shandong University, Jinan, Shandong 250012, P.R. China, Department of Pathology, Shandong Cancer Hospital and Institute, Jinan, Shandong 250117, P.R. China
  • Pages: 871-877
    |
    Published online on: December 16, 2013
       https://doi.org/10.3892/ol.2013.1759
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Abstract

In ovarian cancer patients, chemotherapy resistance is the principal factor restricting long‑term treatment. Paclitaxel (Pac) has been previously reported to be a ligand to Toll‑like receptor 4 (TLR4). It was determined that TLR4 signaling is divided into the following two pathways: Myeloid differentiation factor 88 (MyD88)‑dependent and MyD88‑independent. The present study investigated the effect of TLR4 ligation by Pac in MyD88‑positive (MyD88+) and MyD88‑negative (MyD88‑) human ovarian cancer cell lines. An RNA interference expression vector was specifically constructed to target TLR4 mRNA, which was stably transfected into the human ovarian cancer cell lines (SKOV3, OVCAR3, A2780 and 3AO). Cytokines, including interleukin (IL)‑6 and IL‑8, were detected. Cell proliferation and apoptosis were assessed in the cells transfected with scramble control and TLR4 shRNA to explore the possible functions of TLR4 in ovarian cancer cell growth. It was found that lipopolysaccharide and Pac significantly increase the secretion of IL‑6 and IL‑8 in the SKOV3 cell line. Similarly, Pac resulted in a significant upregulation of IL‑6 and IL‑8 in OVCAR3 cells, but not in A2780 and 3AO cells. These results suggested that in MyD88+ ovarian cancer cell lines, TLR4 depletion shows increased sensitivity to Pac treatment in inhibiting cell proliferation compared with in cells without TLR4 knockdown. On the contrary, such changes were not found in MyD88‑ cells (A2780 and 3AO). TLR4 negatively regulates Pac chemotherapy, particularly in terms of cell proliferation, and TLR4 may be a novel treatment target in Pac‑resistant ovarian cancer.
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1 

Akira S, Uematsu S and Takeuchi O: Pathogen recognition and innate immunity. Cell. 124:783–801. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Takeda K, Kaisho T and Akira S: Toll-like receptors. Annu Rev Immunol. 21:335–376. 2003. View Article : Google Scholar

3 

Yu L and Chen S: Toll-like receptors expressed in tumor cells: targets for therapy. Cancer Immunol Immunother. 57:1271–1278. 2008. View Article : Google Scholar : PubMed/NCBI

4 

Medzhitov R, Preston-Hurlburt P and Janeway CA Jr: A human homologue of the Drosophila Toll protein signals activation of adaptive immunity. Nature. 388:394–397. 1997. View Article : Google Scholar : PubMed/NCBI

5 

Poltorak A, He X, Smirnova I, et al: Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene. Science. 282:2085–2088. 1998. View Article : Google Scholar

6 

Pathak SK, Basu S, Bhattacharyya A, Pathak S, Kundu M and Basu J: Mycobacterium tuberculosis lipoarabinomannan-mediated IRAK-M induction negatively regulates Toll-like receptor-dependent interleukin-12 p40 production in macrophages. J Biol Chem. 280:42794–42800. 2005. View Article : Google Scholar

7 

He W, Liu Q, Wang L, Chen W, Li N and Cao X: TLR4 signaling promotes immune escape of human lung cancer cells by inducing immunosuppressive cytokines and apoptosis resistance. Mol Immunol. 44:2850–2859. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Fallows S, Price J, Atkinson RJ, Johnston PG, Hickey I and Russell SE: P53 mutation does not affect prognosis in ovarian epithelial malignancies. J Pathol. 194:68–75. 2001. View Article : Google Scholar : PubMed/NCBI

9 

Byrd-Leifer CA, Block EF, Takeda K, Akira S and Ding A: The role of MyD88 and TLR4 in the LPS-mimetic activity of Taxol. Eur J Immunol. 31:2448–2457. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Lord KA, Hoffman-Liebermann B and Liebermann DA: Nucleotide sequence and expression of a cDNA encoding MyD88, a novel myeloid differentiation primary response gene induced by IL6. Oncogene. 5:1095–1097. 1990.

11 

Asschert JG, Vellenga E, Ruiters MH and de Vries EG: Regulation of spontaneous and TNF/IFN-induced IL-6 expression in two human ovarian-carcinoma cell lines. Int J Cancer. 82:244–249. 1999. View Article : Google Scholar : PubMed/NCBI

12 

Watson JM, Sensintaffar JL, Berek JS and Martinez-Maza O: Constitutive production of interleukin 6 by ovarian cancer cell lines and by primary ovarian tumor cultures. Cancer Res. 50:6959–6965. 1990.

13 

Wu S, Rodabaugh K, Martinez-Maza O, et al: Stimulation of ovarian tumor cell proliferation with monocyte products inducing interleukin 1, interleukin 6 and tumor necrosis factor-alpha. Am J Obstet Gynecol. 166:977–1007. 1992.PubMed/NCBI

14 

Obata NH, Tamakoshi K, Shibata K, Kikkawa F and Tomoda Y: Effects of interleukin-6 on in vitro cell attachment, migration and invasion of human ovarian carcinoma. Anticancer Res. 17:337–342. 1997.PubMed/NCBI

15 

Nilsson MB, Langley RR and Fidler IJ: Interleukin-6, secreted by human ovarian carcinoma cells, is a potent proangiogenic cytokine. Cancer Res. 65:10794–10800. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Shahzad MM, Arevalo JM, Armaiz-Pena GN, et al: Stress effects on FosB- and interleukin-8 (IL8)-driven ovarian cancer growth and metastasis. J Biol Chem. 285:35462–35470. 2010. View Article : Google Scholar

17 

Kawai T, Adachi O, Ogawa T, Takeda K and Akira S: Unresponsiveness of MyD88-deficient mice to endotoxin. Immunity. 11:115–122. 1999. View Article : Google Scholar : PubMed/NCBI

18 

Björkbacka H, Fitzgerald KA, Huet F, et al: The induction of macrophage gene expression by LPS predominantly utilizes Myd88-independent signaling cascades. Physiol Genomics. 19:319–330. 2004.PubMed/NCBI

19 

Kelly MG, Alvero AB, Chen R, et al: TLR-4 signaling promotes tumor growth and Pac chemoresistance in ovarian cancer. Cancer Res. 66:3859–3868. 2006. View Article : Google Scholar : PubMed/NCBI

20 

Wang AC, Su QB, Wu FX, Zhang XL and Liu PS: Role of TLR4 for Pac chemotherapy in human epithelial ovarian cancer cells. Eur J Clin Invest. 39:157–164. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Mao HL, Liu PS, Zheng JF, et al: Transfection of Smac/DIABLO sensitizes drug-resistant tumor cells to TRAIL or Pac-induced apoptosis in vitro. Pharmacol Res. 56:483–492. 2007. View Article : Google Scholar

22 

Wani MC, Taylor HL, Wall ME, Coggon P and McPhail AT: Plant antitumor agents. VI The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J Am Chem Soc. 93:2325–2327. 1971. View Article : Google Scholar : PubMed/NCBI

23 

Manfredi JJ, Parness J and Horwitz SB: Taxol binds to cellular microtubules. J Cell Biol. 94:688–696. 1982. View Article : Google Scholar

24 

Wang J, Kobayashi M, Han M, et al: MyD88 is involved in thesignalling pathway for Taxol-induced apoptosis and TNF-alpha expression in human myelomonocytic cells. Br J Haematol. 118:638–645. 2002. View Article : Google Scholar : PubMed/NCBI

25 

Zimmer SM, Liu J, Clayton JL, Stephens DS and Snyder JP: Paclitaxelbinding to human and murine MD-2. J Biol Chem. 283:27916–27926. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Ozols RF, Bundy BN, Greer BE, et al: Phase III trial of carboplatin and Paclitaxel compared with cisplatin and Pac in patients with optimally resected stage III ovarian cancer: a Gynecologic Oncology Group study. J Clin Oncol. 21:3194–3200. 2003. View Article : Google Scholar

27 

Song G, Ouyang G and Bao S: The activation of Akt/PKB signaling pathway and cell survival. J Cell Mol Med. 9:59–71. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Ding AH, Porteu F, Sanchez E and Nathan CF: Shared actions of endotoxin and taxol on TNF receptors and TNF release. Science. 248:370–372. 1990. View Article : Google Scholar : PubMed/NCBI

29 

Brint EK, Xu D, Liu H, et al: ST2 is an inhibitor of interleukin 1 receptor and Toll-like receptor 4 signaling and maintains endotoxin tolerance. Nat Immunol. 5:373–379. 2004. View Article : Google Scholar : PubMed/NCBI

30 

Burns K, Janssens S, Brissoni B, Olivos N, Beyaert R and Tschopp J: Inhibition of interleukin 1 receptor/Toll-like receptor signaling through the alternatively spliced, short form of MyD88 is due to its failure to recruit IRAK-4. J Exp Med. 197:263–268. 2003. View Article : Google Scholar

31 

Schmitz I, Kirchhoff S and Krammer PH: Regulation of death receptor-mediated apoptosis pathways. Int J Biochem Cell Biol. 32:1123–1136. 2000. View Article : Google Scholar : PubMed/NCBI

32 

Huang B, Zhao J, Li H, et al: Toll-like receptors on tumor cells facilitate evasion of immune surveillance. Cancer Res. 65:5009–5014. 2005. View Article : Google Scholar : PubMed/NCBI

33 

Pérez-Tomás R: Multidrug resistance: retrospect and prospects in anti-cancer drug treatment. Curr Med Chem. 13:1859–1876. 2006.PubMed/NCBI

34 

Fulda S and Debatin KM: Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene. 25:4798–4811. 2006. View Article : Google Scholar : PubMed/NCBI

35 

Nakanishi C and Toi M: Nuclear factor-kappaB inhibitors as sensitizers to anticancer drugs. Nat Rev Cancer. 5:297–309. 2005. View Article : Google Scholar : PubMed/NCBI

36 

Silasi DA, Alvero AB, Illuzzi J, et al: MyD88 predicts chemoresistance to Pac in epithelial ovarian cancer. Yale J Biol Med. 79:153–163. 2006.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang AC, Ma YB, Wu FX, Ma ZF, Liu NF, Gao R, Gao YS and Sheng XG: TLR4 induces tumor growth and inhibits paclitaxel activity in MyD88‑positive human ovarian carcinoma in vitro. Oncol Lett 7: 871-877, 2014.
APA
Wang, A., Ma, Y., Wu, F., Ma, Z., Liu, N., Gao, R. ... Sheng, X. (2014). TLR4 induces tumor growth and inhibits paclitaxel activity in MyD88‑positive human ovarian carcinoma in vitro. Oncology Letters, 7, 871-877. https://doi.org/10.3892/ol.2013.1759
MLA
Wang, A., Ma, Y., Wu, F., Ma, Z., Liu, N., Gao, R., Gao, Y., Sheng, X."TLR4 induces tumor growth and inhibits paclitaxel activity in MyD88‑positive human ovarian carcinoma in vitro". Oncology Letters 7.3 (2014): 871-877.
Chicago
Wang, A., Ma, Y., Wu, F., Ma, Z., Liu, N., Gao, R., Gao, Y., Sheng, X."TLR4 induces tumor growth and inhibits paclitaxel activity in MyD88‑positive human ovarian carcinoma in vitro". Oncology Letters 7, no. 3 (2014): 871-877. https://doi.org/10.3892/ol.2013.1759
Copy and paste a formatted citation
x
Spandidos Publications style
Wang AC, Ma YB, Wu FX, Ma ZF, Liu NF, Gao R, Gao YS and Sheng XG: TLR4 induces tumor growth and inhibits paclitaxel activity in MyD88‑positive human ovarian carcinoma in vitro. Oncol Lett 7: 871-877, 2014.
APA
Wang, A., Ma, Y., Wu, F., Ma, Z., Liu, N., Gao, R. ... Sheng, X. (2014). TLR4 induces tumor growth and inhibits paclitaxel activity in MyD88‑positive human ovarian carcinoma in vitro. Oncology Letters, 7, 871-877. https://doi.org/10.3892/ol.2013.1759
MLA
Wang, A., Ma, Y., Wu, F., Ma, Z., Liu, N., Gao, R., Gao, Y., Sheng, X."TLR4 induces tumor growth and inhibits paclitaxel activity in MyD88‑positive human ovarian carcinoma in vitro". Oncology Letters 7.3 (2014): 871-877.
Chicago
Wang, A., Ma, Y., Wu, F., Ma, Z., Liu, N., Gao, R., Gao, Y., Sheng, X."TLR4 induces tumor growth and inhibits paclitaxel activity in MyD88‑positive human ovarian carcinoma in vitro". Oncology Letters 7, no. 3 (2014): 871-877. https://doi.org/10.3892/ol.2013.1759
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