Combined effects of XAF1 and TRAIL on the apoptosis of lung adenocarcinoma cells

Zhang,Fuquan; Chen,Donglai; Yang,Wentao; Duan,Shanzhou; Chen,Yongbing

doi:10.3892/etm.2019.7491

Combined effects of XAF1 and TRAIL on the apoptosis of lung adenocarcinoma cells

Authors:
- Fuquan Zhang
- Donglai Chen
- Wentao Yang
- Shanzhou Duan
- Yongbing Chen
View Affiliations

Affiliations: Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China, Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai 200433, P.R. China
Published online on: April 16, 2019 https://doi.org/10.3892/etm.2019.7491
Pages: 4663-4669

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

This study aimed to investigate the effects and mechanisms of X‑linked inhibitor of apoptosis protein (XIAP)‑associated factor 1 (XAF1) and tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) on the apoptosis of A549 lung adenocarcinoma cell lines. Recombinant lentiviral vector of Ad5/F35‑XAF1 and controlled lentiviral vector of Ad5/F35‑Null were transfected into A549 cells at same multiplicity of infection (MOI), respectively. Based on whether recombinant human TRAIL (rhTRAIL) was added or not, cells were divided into different groups as follows: XAF1 group, XAF1 + TRAIL group, XAF1‑Null group, and XAF1‑Null + TRAIL group. Following culturing for 48 h, the mRNA and protein expression levels of related genes were determined by reverse transcription‑quantitative polymerase chain reaction and western blotting analyses, respectively. Cell proliferationand cell apoptosis were detected by MTT assay and Annexin V‑FITC/PI double staining, respectively. Xenograft mice models were established with A549 lung adenocarcinoma cells and treated with recombinant virus Ad5/F35‑XAF1 and controlled virus Ad5/F35‑Null for immunohistochemical analysis. Expression levels of XAFl at the mRNA and protein levels were significantly higher in the XAF1 group and XAF1 + TRAIL groups when compared with the levels in the other groups (P<0.05). Cleavage of apoptosis‑associated proteins, poly ADP‑ribose polymerase and caspase‑3, was noted in the XAF1 + TRAIL group, whereas they were not detected in other groups. Apoptosis rates of A549 cells in the XAF1, Null + TRAIL and XAFl + TRAIL groups were significantly higher than those in the NOR and Null groups (P<0.05). Apoptotic rates were highest in the XAF1 + TRAIL group. In conclusion, these findings suggest that combined use of XAF1 and TRAIL may synergistically induce the apoptosis of A549 lung adenocarcinoma cells.

View Figures

View References

1	Jemal A, Bray F, Center MM, Ferlay J, Ward E and Forman D: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar : PubMed/NCBI
2	Lockshin RA and Williams CM: Programmed cell death-I. Cytology of degeneration in the intersegmental muscles of the Pernyi silkmoth. J Insect Physiol. 11:123–133. 1965. View Article : Google Scholar : PubMed/NCBI
3	Hanahan D and Weinberg RA: The hallmarks of cancer. Cell. 100:57–70. 2000. View Article : Google Scholar : PubMed/NCBI
4	Yan F, Gou L, Yang J, Chen L, Tong A, Tang M, Yuan Z, Yao S, Zhang P and Wei Y: A novel pro-apoptosis gene PNAS4 that induces apoptosis in A549 human lung adenocarcinoma cells and inhibits tumor growth in mice. Biochimie. 91:502–507. 2009. View Article : Google Scholar : PubMed/NCBI
5	Yang WT, Chen DL, Zhang FQ, Xia YC, Zhu RY, Zhou DS and Chen YB: Experimental study on inhibition effects of the XAF1 gene against lung cancer cell proliferation. Asian Pac J Cancer Prev. 15:7825–7829. 2014. View Article : Google Scholar : PubMed/NCBI
6	Yang WT, Chen DL, Zhang FQ, Xia YC, Zhu RY, Zhou DS and Chen YB: Experimental study on inhibition effects of the XAF1 gene against lung cancer cell proliferation. Asian Pac J Cancer Prev. 15:7825–7829. 2014. View Article : Google Scholar : PubMed/NCBI
7	Ashkenazi A, Pai RC, Fong S, Leung S, Lawrence DA, Marsters SA, Blackie C, Chang L, McMurtrey AE, Hebert A, et al: Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest. 104:155–162. 1999. View Article : Google Scholar : PubMed/NCBI
8	Hao C, Song JH, Hsi B, Lewis J, Song DK, Petruk KC, Tyrrell DL and Kneteman NM: TRAIL inhibits tumor growth but is nontoxic to human hepatocytes in chimeric mice. Cancer Res. 64:8502–8506. 2004. View Article : Google Scholar : PubMed/NCBI
9	Lawrence D, Shahrokh Z, Marsters S, Achilles K, Shih D, Mounho B, Hillan K, Totpal K, DeForge L, Schow P, et al: Differential hepatocyte toxicity of recombinant Apo2L/TRAIL versions. Nat Med. 7:383–385. 2001. View Article : Google Scholar : PubMed/NCBI
10	Arrieta O, Saavedra-Perez D, Kuri R, Aviles-Salas A, Martinez L, Mendoza-Posada D, Castillo P, Astorga A, Guzman E and De la Garza J: Brain metastasis development and poor survival associated with carcinoembryonic antigen (CEA) level in advanced non-small cell lung cancer: A prospective analysis. BMC Cancer. 9:1192009. View Article : Google Scholar : PubMed/NCBI
11	Brown JM and Attardi LD: The role of apoptosis in cancer development and treatment response. Nat Rev Cancer. 5:231–237. 2005. View Article : Google Scholar : PubMed/NCBI
12	Liston P, Fong WG and Korneluk RG: The inhibitors of apoptosis: There is more to life than Bcl2. Oncogene. 22:8568–8580. 2003. View Article : Google Scholar : PubMed/NCBI
13	Straszewski-Chavez SL, Visintin IP, Karassina N, Los G, Liston P, Halaban R, Fadiel A and Mor G: XAF1 mediates tumor necrosis factor-alpha-induced apoptosis and X-linked inhibitor of apoptosis cleavage by acting through the mitochondrial pathway. J BiolChem. 282:13059–13072. 2007.
14	Fong WG, Liston P, Rajcan-Separovic E, St Jean M, Craig C and Korneluk RG: Expression and genetic analysis of XIAP-associated factor 1 (XAF1) in cancer cell lines. Genomics. 70:113–122. 2000. View Article : Google Scholar : PubMed/NCBI
15	Finnberg N and El-Deiry WS: Selective TRAIL-induced apoptosis in dysplastic neoplasia of the colon may lead to new neoadjuvant or adjuvant therapies. Clin Cancer Res. 12:4132–4136. 2006. View Article : Google Scholar : PubMed/NCBI
16	Jalving M, de Jong S, Koornstra JJ, Boersma-van Ek W, Zwart N, Wesseling J, de Vries EG and Kleibeuker JH: TRAIL induces apoptosis in human colorectal adenoma cell lines and human colorectal adenomas. Clin Cancer Res. 12:4350–4356. 2006. View Article : Google Scholar : PubMed/NCBI
17	Zhang L and Fang B: Mechanisms of resistance to TRAIL-induced apoptosis in cancer. Cancer Gene Ther. 12:228–237. 2005. View Article : Google Scholar : PubMed/NCBI
18	Herbst RS, Mendolson DS, Ebbinghaus S, Gordon MS, O'Dwyer P, Lieberman G, Ing J, Kurzrock R, Novotny W and Eckhardt G: A phase I safety and pharmacokinetic (PK) study of recombinant Apo2L/TRAIL, an apoptosis-inducing protein in patients with advanced cancer. J ClinOncol. 24:1242006.
19	Soria JC, Mark Z, Zatloukal P, Szima B, Albert I, Juhász E, Pujol JL, Kozielski J, Baker N, Smethurst D, et al: Randomized phase II study of dulanermin in combination with paclitaxel, carboplatin, and bevacizumab in advanced non-small-cell lung cancer. J Clin Oncol. 29:4442–4451. 2011. View Article : Google Scholar : PubMed/NCBI
20	Yee L, Fanale M, Dimick K, Calvert S, Robins C, Ing J, Ling J, Novotny W, Ashkenazi A and Burris H: A phase IB safety and pharmacokinetic (PK) study of recombinant human Apo2L/TRAIL in combination with rituximab in patients with low-grade non-Hodgkin lymphoma. J ClinOncol. 25:80782007.
21	Tu SP, Liston P, Cui JT, Lin MC, Jiang XH, Yang Y, Gu Q, Jiang SH, Lum CT, Kung HF, et al: Restoration of XAF1 expression induces apoptosis and inhibits tumor growth in gastric cancer. Int J Cancer. 125:688–697. 2009. View Article : Google Scholar : PubMed/NCBI
22	Tu SP, Sun YW, Cui JT, Zou B, Lin MC, Gu Q, Jiang SH, Kung HF, Korneluk RG and Wong BC: Tumor suppressor XIAP-associated factor 1 (XAF1) cooperates with tumor necrosis factor-related apoptosis-inducing ligand to suppress colon cancer growth and trigger tumor regression. Cancer. 116:1252–1263. 2010. View Article : Google Scholar : PubMed/NCBI
23	Alnemri ES, Livingston DJ, Nicholson DW, Salvesen G, Thornberry NA, Wong WW and Yuan J: Human ICE/CED-3 protease nomenclature. Cell. 87:1711996. View Article : Google Scholar : PubMed/NCBI
24	Cohen GM: Caspases: The executioners of apoptosis. Biochem J. 326:1–16. 1997. View Article : Google Scholar : PubMed/NCBI
25	Wang J and Lenardo MJ: Roles of caspases in apoptosis, development, and cytokine maturation revealed by homozygous gene deficiencies. J Cell Sci. 113:753–757. 2000.PubMed/NCBI
26	Tewari M, Quan LT, O'Rourke K, Desnoyers S, Zeng Z, Beidler DR, Poirier GG, Salvesen GS and Dixit VM: Yama/CPP32beta, a mammalian homolog of CED-3, is a CrmA-inhibitable protease that cleaves the death substrate poly(ADP-ribose) polymerase. Cell. 81:801–809. 1995. View Article : Google Scholar : PubMed/NCBI
27	Virág L, Robaszkiewicz A, Rodriguez-Vargas JM and Oliver FJ: Poly(ADP-ribose) signaling in cell death. Mol Aspects Med. 34:1153–1167. 2013. View Article : Google Scholar : PubMed/NCBI