All-trans retinoic acid promotes apoptosis effect of tumor necrosis factor related apoptosis induced ligand on a variety of pancreatic cancer cells

doi:10.16138/j.1673-6087.2023.03.007

Abstract

Abstract:

Objective To observe whether all trans retinoic acid (ATRA) can promote the apoptosis effect of tumor necrosis factor related apoptosis induced ligand (TRAIL) on various pancreatic cancer cells. Methods The pCA13 plasmid carrying TRAIL gene was transfected into three types of pancreatic cancer cell SW1990, Patu8988 and Bx-PC3 respectively. ATRA or equivalent solvent was added after 24 h of transfection. The cell viability was measured by the methyl thiazolyl tetrazolium(MTT) method, apoptosis rates and the expression of TRAIL receptor R1 and R2 were detected by flow cytometry, and the apoptosis was observed by terminal deoxynucleotidyl transferase(TdT) mediated dUTP nick end labeling (TUNEL) and Hoechst double staining and transmission electron microscopy. Results The cell viability of the TRAIL+ATRA group was significantly inhibited compared to the group without ATRA (P<0.05). The result of the flow cytometry showed that ATRA significantly promoted cell apoptosis compared with the group without ATRA(P<0.05). Apoptosis was observed by transmission electron microscopy after TUNEL and Hoechst double staining. However, there was no significant difference in expression of TRAIL-R1 and R2 between the TRAIL+ATRA group and the non-ATRA group(P>0.05). Conclusions ATRA can promote the apoptosis of TRAIL on various pancreatic cancer cells, and its mechanism is not related to the up-regulation of TRAIL-R1 and R2.

Key words: All trans retinoic acid, Tumor necrosis factor related apoptosis induced ligand, Pancreatic cancer, Apoptosis

CLC Number:

R735.9

ZHU Ying, TANG Yuming, HUANG Jia, ZHANG Yongping, YAO Weiyan. All-trans retinoic acid promotes apoptosis effect of tumor necrosis factor related apoptosis induced ligand on a variety of pancreatic cancer cells[J]. Journal of Internal Medicine Concepts & Practice, 2023, 18(03): 171-176.

Figures/Tables 7

References 10

[1]	朱颖, 汤玉茗, 黄佳, 等. 肿瘤坏死因子相关凋亡诱导配体对胰腺癌细胞凋亡的影响[J]. 中华胰腺病杂志, 2019, 19(3): 198-201.
[2]	Kretz AL, von Karstedt S, Hillenbrand A, et al. Should we keep walking along the trail for pancreatic cancer treatment?[J]. Cancers (Basel), 2018, 10(3): 77. doi: 10.3390/cancers10030077 URL
[3]	Farooqi AA, Zahid R, Maryam A, et al. TRAIL mediated signaling as a double-edged sword in pancreatic cancer[J]. Cell Mol Biol (Noisy-le-grand), 2020, 66(3): 215-220. doi: 10.14715/cmb/2020.66.3.35 URL
[4]	Kim JH, Kim MJ, Choi KC, et al. Quercetin sensitizes pancreatic cancer cells to TRAIL-induced apoptosis through JNK-mediated cFLIP turnover[J]. Int J Biochem Cell Biol, 2016, 78:327-334. doi: S1357-2725(16)30207-2 pmid: 27477310
[5]	Hu Y, Li R, Jin J, et al. Quercetin improves pancreatic cancer chemo-sensitivity by regulating oxidative-inflammatory networks[J]. J Food Biochem, 2022, 46(12): e14453.
[6]	Huang M, Zhu H, Yi C, et al. A novel TRAIL mutant-TRAIL-Mu3 enhances the antitumor effects by the increased affinity and the up-expression of DR5 in pancreatic cancer[J]. Cancer Chemother Pharmacol, 2018, 82(5): 829-838. doi: 10.1007/s00280-018-3658-9
[7]	Ben Khaled N, Hammer K, Ye L, et al. TRAIL receptor targeting agents potentiate PARP inhibitor efficacy in pancreatic cancer independently of BRCA2 mutation status[J]. Cancers (Basel), 2022, 14(21): 5240. doi: 10.3390/cancers14215240 URL
[8]	Huang X, Ou C, Shu Y, et al. A self-sustained nanoplatform reverses TRAIL-resistance of pancreatic cancer through coactivating of exogenous and endogenous apoptotic pathway[J]. Biomaterials, 2021, 272:120795. doi: 10.1016/j.biomaterials.2021.120795 URL
[9]	Hu W, Jia X, Gao Y, et al. Chaetospirolactone reverses the apoptotic resistance towards TRAIL in pancreatic cancer[J]. Biochem Biophys Res Commun, 2018, 495(1): 621-628. doi: 10.1016/j.bbrc.2017.10.144 URL
[10]	Dai H, Jiang Y, Luo Y, et al. Triptolide enhances TRAIL sensitivity of pancreatic cancer cells by activating autophagy via downregulation of PUM1[J]. Phytomedicine, 2019, 62: 152953. doi: 10.1016/j.phymed.2019.152953 URL

细胞株转染时间	pCA13/TRAIL 质粒组	pCA13/TRAIL 质粒+ATRA组	t	P
SW1990
48 h	9.77±5.56	27.52±6.29	3.663 1	0.021 5
72 h	21.81±1.70	40.35±4.19	7.110 4	0.002 1
Patu8988
48 h	15.65±2.42	25.82±3.13	4.453 6	0.011 2
72 h	16.98±2.27	40.68±1.90	13.851 5	0.000 2
Bx-PC3
48 h	15.04±5.28	28.91±4.05	3.607 4	0.022 6
72 h	18.20±5.18	55.04±2.47	11.116 0	0.000 4

各细胞株作用时间	未转染组凋亡率	pCA13空质粒组凋亡率	pCA13/TRAIL质粒组凋亡率	空质粒+ATRA 组凋亡率	pCA13/TRAIL质粒+ATRA组凋亡率	F	P
SW1990
48 h	7.11±1.88	10.58±1.88^1）	27.30±5.14^1）	24.72±6.19	42.03±4.05	33.527	0.000 009
72 h	8.65±0.71	12.46±2.14^1）	31.45±4.93^1）	34.77±10.62	52.56±2.74	31.999	0.000 011
Patu8988
48 h	4.88±2.10	8.42±0.46^1）	13.52±0.95^1）	13.33±1.05	19.62±1.97	44.847	0.000 002
72 h	7.62±0.39	8.51±0.21^1）	14.43±3.13^1）	17.50±8.52	23.21±3.27	6.757	0.006 680
Bx-PC3
48 h	4.97±0.40	16.11±1.66^1）	31.40±8.70^1）	40.45±11.28	53.31±6.28	22.500	0.000 055
72 h	11.40±1.97	20.39±3.00^1）	43.48±5.76^1）	41.18±5.50	58.98±6.36	46.752	0.000 002

各细胞株作用时间	空质粒组	pCA13/TRAIL 质粒组	pCA13/TRAIL 质粒+ATRA组	P
SW1990
48 h	39.85±7.69	61.37±3.05	64.97±4.68	0.051
72 h	35.37±5.91	55.28±4.41	61.32±4.43	0.051
Patu8988
48 h	31.36±4.31	42.10±5.11	42.94±4.44	0.061
72 h	29.65±1.57	48.0±10.46	51.54±13.79	0.066
Bx-PC3
48 h	25.99±3.76	36.64±4.84	33.79±3.92	0.051
72 h	24.96±3.36	33.52±4.49	32.54±3.77	0.061

各细胞株作用时间	空质粒组	pCA13/TRAIL 质粒组	pCA13/TRAIL 质粒+ATRA组	P
SW1990
48 h	23.62±4.62	36.20±4.83^1）	39.03±3.24^1）	0.010
72 h	21.22±1.96	30.36±4.49^1）	38.03±6.14^1）	0.011
Patu8988
48 h	29.04±3.81	37.26±8.46	44.85±2.76^1）	0.037
72 h	28.01±3.36	42.32±9.25	49.66±8.01^1）	0.029
Bx-PC3
48 h	15.90±3.19	24.32±3.71^1）	28.88±3.11^1）	0.009
72 h	17.00±0.87	23.98±1.60^1）	27.33±4.73^1）	0.013

[1]	SHANG Siyu, XIANG Yang, PAN Bohan, et a. Biological effects of alginate oligosaccharides on wound: Degree of lysis dependence [J]. Journal of Tissue Engineering and Reconstructive Surgery, 2023, 19(1): 1-.
[2]	YANG Ruixin, DU Yutong, YAN Ranlin, ZHU Zhenggang, LI Chen, YU Yingyan. Improving exploration of biological sample pretreatment in single-cell transcriptome sequencing of gastrointestinal tumors [J]. Journal of Diagnostics Concepts & Practice, 2022, 21(05): 567-574.
[3]	LU Weihui, LIU Wei, WANG Cong, WANG Zhenglin. Effects of CXCR2 on invasion, migration and apoptosis of gastric cancer cells [J]. Journal of Surgery Concepts & Practice, 2021, 26(5): 430-436.
[4]	ZHU Yingying, ZHANG Jiaojiao, SUN Junnan, WANG Hairong. Effect of chloroquine on type Ⅱ alveolar cell injury caused by lipopolysaccharide [J]. Journal of Internal Medicine Concepts & Practice, 2021, 16(03): 197-201.
[5]	LI Xiaoli, LI Weiguang, QIAN Aihua, CAO Guoliang. The serum level of microRNA-486-3p and its effects on proliferation and apoptosis of pancreatic cancer cells [J]. Journal of Internal Medicine Concepts & Practice, 2021, 16(02): 121-125.
[6]	ZHA Qing, YU Chenxi, LIU Ya, YANG Ling, YE Jiawen, LIU Yan. Preliminary study on the role of miR-16 in progression of coronary atherosclerosis and possible molecular mechanism [J]. Journal of Diagnostics Concepts & Practice, 2021, 20(01): 82-87.
[7]	DING Fangmi, LIU Zhendong. Forkhead box D1 promotes invasion and metastasis of pancreatic cancer via extracellular signal-regulated kinase pathway [J]. Journal of Surgery Concepts & Practice, 2020, 25(06): 486-492.
[8]	WU Jingyi, LI Guojing, FEI Jian. Acute pancreatitis as first episode of pancreatic cancer: a report of 17 cases [J]. Journal of Surgery Concepts & Practice, 2020, 25(04): 326-330.
[9]	. [J]. Journal of Internal Medicine Concepts & Practice, 2020, 15(02): 111-115.
[10]	SONG Ahui,TONG Yan,LIU Yingli. Effectiveness of BK Channel Inhibitor on Proliferation,Apoptosis and Cytokines of Mesenchymal Stem Cells Derived from Human Umbilical Cord Wharton's Jelly [J]. Journal of Tissue Engineering and Reconstructive Surgery, 2019, 15(1): 5-9.
[11]	YAN Cheng, NI Xiaoyan, YAO Xiuzhong, CHEN Caizhong, GU Junying. Diagnostic value of free-breath diffusion-weighted MR imaging in autoimmune pancreatitis and pancreatic cancer [J]. Journal of Surgery Concepts & Practice, 2019, 24(03): 230-235.
[12]	ZHAO Zhifeng, XIE Rongli, SHEN Dongjie, ZHANG Jun, XU Zhiwei, CHENG Dongfeng, FEI Jian, DENG Xiaxing, SHEN Baiyong, PENG Chenghong. Study on salivary tumor markers in diagnosis of pancreatic cancer [J]. Journal of Surgery Concepts & Practice, 2019, 24(02): 149-154.
[13]	. [J]. Journal of Internal Medicine Concepts & Practice, 2019, 14(02): 121-126.
[14]	CHENG Yanyong,WANG Jiayi,JIANG Yunfeng,SUN Yu. Effects of Bone Marrow Mesenchymal Stem Cells on Sevoflurane-Induced Apoptosis and Cell Viability of Primary Cultured Neuron [J]. Journal of Tissue Engineering and Reconstructive Surgery, 2018, 14(1): 24-27.
[15]	ZHU Qingfeng, HU Xiaoli, ZHU Jianyi, LANG Wenjing, ZHONG Jihua, CHEN Fangyuan. Study on mechanism of synergistic effect of ASP2215 combined with SAHA on FLT3-ITD mutant cell line [J]. Journal of Diagnostics Concepts & Practice, 2018, 17(05): 538-546.