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TRAIL mutant membrane penetrating peptide alike-MuR6-TR enhances the antitumor effects of TRAIL in pancreatic carcinoma both in vitro and in vivo

  • Authors:
    • Lei Sun
    • Chen Chen
    • Aijing Zhu
    • Ying Huang
    • Hong Zhu
    • Cheng Yi
  • View Affiliations / Copyright

    Affiliations: Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R. China, Department of Pathophysiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan 610041, P.R. China
    Copyright: © Sun et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1468-1476
    |
    Published online on: April 26, 2017
       https://doi.org/10.3892/ijmm.2017.2968
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Abstract

To remedy the drug resistance of natural tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and enhance its antitumor effects, we prepared a type of TRAIL mutant membrane penetrating peptide alike (TMPPA)‑TRAIL mutant R6 (MuR6-TR) by mutating the N‑terminal of the soluble TRAIL gene sequence. The expressed MuR6‑TR protein was purified to treat pancreatic carcinoma cell lines BxPC‑3 and PANC‑1. The inhibitory effects on the proliferation of BxPC‑3 and PANC‑1 cells was assessed with CCK‑8 assay and compared with natural TRAIL. The antitumor effect of MuR6‑TR was assessed on implant tumors derived from PANC‑1 cells in nude mice and compared with gemcitabine. Finally, the soluble MuR6‑TR gene was successfully mutated with 4 amino acids in the N‑terminal of TRAIL and had a molecular size of 513 bp. The mutant MuR6‑TR was connected to pET32a and verified by enzymatic digestion and sequencing. The recombinant MuR6‑TR was transformed and expressed in Escherichia coli. The CCK‑8 assay results indicated that MuR6‑TR inhibited the growth of BxPC‑3 and PANC‑1 cells in a dose‑dependent manner, with IC50 values of 4.63 and 7.84 ng/ml, respectively, which were much lower than that of natural TRAIL. MuR6‑TR demonstrated a higher inhibitory effect on tumor growth (24.2%) than natural TRAIL (14.4%) and an effect similar to that of gemcitabine at an early period. Thus, the mutant MuR6‑TR exhibited a stronger antitumor effect than that of natural TRAIL both in vivo and in vitro and may have potential therapeutic value for pancreatic carcinoma, which requires further validation.
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1 

Singh D, Upadhyay G, Srivastava RK and Shankar S: Recent advances in pancreatic cancer: Biology, treatment, and prevention. Biochim Biophys Acta. 1856:13–27. 2015.PubMed/NCBI

2 

Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Boatright KM, Renatus M, Scott FL, Sperandio S, Shin H, Pedersen IM, Ricci JE, Edris WA, Sutherlin DP, Green DR, et al: A unified model for apical caspase activation. Mol Cell. 11:529–541. 2003. View Article : Google Scholar : PubMed/NCBI

4 

Arlt A, Müerköster SS and Schäfer H: Targeting apoptosis pathways in pancreatic cancer. Cancer Lett. 332:346–358. 2013. View Article : Google Scholar

5 

Ashkenazi A: Targeting death and decoy receptors of the tumour-necrosis factor superfamily. Nat Rev Cancer. 2:420–430. 2002. View Article : Google Scholar : PubMed/NCBI

6 

Di Pietro R and Zauli G: Emerging non-apoptotic functions of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)/Apo2L. J Cell Physiol. 201:331–340. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Liu H, Zeng F, Zhang M, Huang F, Wang J, Guo J, Liu C and Wang H: Emerging landscape of cell penetrating peptide in reprogramming and gene editing. J Control Release. 226:124–137. 2016. View Article : Google Scholar : PubMed/NCBI

8 

Joseph SC, Blackman BA, Kelly ML, Phillips M, Beaury MW, Martinez I, Parronchi CJ, Bitsaktsis C, Blake AD and Sabatino D: Synthesis, characterization, and biological activity of poly(arginine)-derived cancer-targeting peptides in HepG2 liver cancer cells. J Pept Sci. 20:736–745. 2014. View Article : Google Scholar : PubMed/NCBI

9 

Wang W, Zhang N, Zhao T, Liu M, Zhang T and Li D: Inhibition of tumor growth by polyarginine-fused mutant cytosine deaminase. Appl Biochem Biotechnol. 175:1633–1643. 2015. View Article : Google Scholar

10 

Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA, et al: Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity. 3:673–682. 1995. View Article : Google Scholar : PubMed/NCBI

11 

Cha SS, Song YL and Oh BH: Specificity of molecular recognition learned from the crystal structures of TRAIL and the TRAIL:sDR5 complex. Vitam Horm. 67:1–17. 2004. View Article : Google Scholar : PubMed/NCBI

12 

Alhakamy NA, Dhar P and Berkland CJ: Charge Type, Charge Spacing, and Hydrophobicity of Arginine-Rich Cell-Penetrating Peptides Dictate Gene Transfection. Mol Pharm. 13:1047–1057. 2016. View Article : Google Scholar : PubMed/NCBI

13 

Fujita T, Furuhata M, Hattori Y, Kawakami H, Toma K and Maitani Y: High gene delivery in tumor by intratumoral injection of tetraarginine-PEG lipid-coated protamine/DNA. J Control Release. 129:124–127. 2008. View Article : Google Scholar : PubMed/NCBI

14 

Papaneophytou CP and Kontopidis GA: Optimization of TNF-α overexpression in Escherichia coli using response surface methodology: Purification of the protein and oligomerization studies. Protein Expr Purif. 86:35–44. 2012. View Article : Google Scholar : PubMed/NCBI

15 

Eiteman MA and Altman E: Overcoming acetate in Escherichia coli recombinant protein fermentations. Trends Biotechnol. 24:530–536. 2006. View Article : Google Scholar : PubMed/NCBI

16 

Ozawa F, Friess H, Kleeff J, Xu ZW, Zimmermann A, Sheikh MS and Büchler MW: Effects and expression of TRAIL and its apoptosis-promoting receptors in human pancreatic cancer. Cancer Lett. 163:71–81. 2001. View Article : Google Scholar : PubMed/NCBI

17 

Stadel D, Mohr A, Ref C, MacFarlane M, Zhou S, Humphreys R, Bachem M, Cohen G, Möller P, Zwacka RM, et al: TRAIL-induced apoptosis is preferentially mediated via TRAIL receptor 1 in pancreatic carcinoma cells and profoundly enhanced by XIAP inhibitors. Clin Cancer Res. 16:5734–5749. 2010. View Article : Google Scholar : PubMed/NCBI

18 

Stuckey DW and Shah K: TRAIL on trial: Preclinical advances in cancer therapy. Trends Mol Med. 19:685–694. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Maksimovic-Ivanic D, Stosic-Grujicic S, Nicoletti F and Mijatovic S: Resistance to TRAIL and how to surmount it. Immunol Res. 52:157–168. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Humphreys RC and Halpern W: Trail receptors: Targets for cancer therapy. Adv Exp Med Biol. 615:127–158. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Ashkenazi A, Holland P and Eckhardt SG: Ligand-based targeting of apoptosis in cancer: The potential of recombinant human apoptosis ligand 2/Tumor necrosis factor-related apoptosis-inducing ligand (rhApo2L/TRAIL). J Clin Oncol. 26:3621–3630. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Vogler M, Dürr K, Jovanovic M, Debatin KM and Fulda S: Regulation of TRAIL-induced apoptosis by XIAP in pancreatic carcinoma cells. Oncogene. 26:248–257. 2007. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Sun L, Chen C, Zhu A, Huang Y, Zhu H and Yi C: TRAIL mutant membrane penetrating peptide alike-MuR6-TR enhances the antitumor effects of TRAIL in pancreatic carcinoma both in vitro and in vivo. Int J Mol Med 39: 1468-1476, 2017.
APA
Sun, L., Chen, C., Zhu, A., Huang, Y., Zhu, H., & Yi, C. (2017). TRAIL mutant membrane penetrating peptide alike-MuR6-TR enhances the antitumor effects of TRAIL in pancreatic carcinoma both in vitro and in vivo. International Journal of Molecular Medicine, 39, 1468-1476. https://doi.org/10.3892/ijmm.2017.2968
MLA
Sun, L., Chen, C., Zhu, A., Huang, Y., Zhu, H., Yi, C."TRAIL mutant membrane penetrating peptide alike-MuR6-TR enhances the antitumor effects of TRAIL in pancreatic carcinoma both in vitro and in vivo". International Journal of Molecular Medicine 39.6 (2017): 1468-1476.
Chicago
Sun, L., Chen, C., Zhu, A., Huang, Y., Zhu, H., Yi, C."TRAIL mutant membrane penetrating peptide alike-MuR6-TR enhances the antitumor effects of TRAIL in pancreatic carcinoma both in vitro and in vivo". International Journal of Molecular Medicine 39, no. 6 (2017): 1468-1476. https://doi.org/10.3892/ijmm.2017.2968
Copy and paste a formatted citation
x
Spandidos Publications style
Sun L, Chen C, Zhu A, Huang Y, Zhu H and Yi C: TRAIL mutant membrane penetrating peptide alike-MuR6-TR enhances the antitumor effects of TRAIL in pancreatic carcinoma both in vitro and in vivo. Int J Mol Med 39: 1468-1476, 2017.
APA
Sun, L., Chen, C., Zhu, A., Huang, Y., Zhu, H., & Yi, C. (2017). TRAIL mutant membrane penetrating peptide alike-MuR6-TR enhances the antitumor effects of TRAIL in pancreatic carcinoma both in vitro and in vivo. International Journal of Molecular Medicine, 39, 1468-1476. https://doi.org/10.3892/ijmm.2017.2968
MLA
Sun, L., Chen, C., Zhu, A., Huang, Y., Zhu, H., Yi, C."TRAIL mutant membrane penetrating peptide alike-MuR6-TR enhances the antitumor effects of TRAIL in pancreatic carcinoma both in vitro and in vivo". International Journal of Molecular Medicine 39.6 (2017): 1468-1476.
Chicago
Sun, L., Chen, C., Zhu, A., Huang, Y., Zhu, H., Yi, C."TRAIL mutant membrane penetrating peptide alike-MuR6-TR enhances the antitumor effects of TRAIL in pancreatic carcinoma both in vitro and in vivo". International Journal of Molecular Medicine 39, no. 6 (2017): 1468-1476. https://doi.org/10.3892/ijmm.2017.2968
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