Effect of lysophosphatidic acid on hepatoma cells and related mechanism

Yanying ZHAO; Zhenqi HAN; Yanping ZOU; Yunpeng LI; Tao XU; Liyan LIU; Haitao CHENG

doi:10.3969/j.issn.1001-5256.2023.11.016

Volume 39 Issue 11

Nov. 2023

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Article Navigation > Journal of Clinical Hepatology > 2023 > 39(11): 2623-2628

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Effect of lysophosphatidic acid on hepatoma cells and related mechanism

DOI: 10.3969/j.issn.1001-5256.2023.11.016

1.
Department of Gastrointestinal Endoscopy，The Affiliated Hospital of Changchun University of Traditional Chinese Medicine，Changchun 130021，China
2.
Department of Gastroenterology，The FAW General Hospital of Jilin Province，Changchun 130011，China

Research funding:

Project of Jilin Provincial Health and Health Commission (2021LC093)

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Corresponding author: CHENG Haitao， yychenghaitao@foxmail.com （ORCID： 0009-0004-2693-0449）
Received Date: 2023-02-09
Accepted Date: 2023-04-13
Published Date: 2023-11-28

Abstract

Abstract

Objective To investigate the expression of lysophosphatidic acid （LPA） in patients with liver cancer， as well as its influence on malignant biological behavior of liver cancer and related regulatory mechanism. Methods From January 2016 to December 2022， 26 patients with liver cancer， 28 patients with liver cirrhosis， and 28 individuals undergoing physical examination were enrolled. ELISIA was used to measure the content of LPA in plasma and peritoneal effusion of the patients with liver cancer or liver cirrhosis accompanied by peritoneal effusion， and the content of LPA was measured in plasma of the normal population at the same time， so as to clarify the difference in the expression of LPA in different populations， such as the patients with liver cancer and those with liver cirrhosis. MTT cell proliferation assay and cell migration assay were used to observe the influence of LPA and its inhibitor pertussis toxin （PTX） on the proliferation， migration， and invasion of SMMC7721 cells. In order to investigate the effect of LPA on the expression of RhoA and its upstream and downstream molecules FAK and P53 after binding to its receptor， qPCR and Western blot were used to observe the effect of LPA on the mRNA and protein expression levels of P53， FAK， and RhoA in SMMC7721 cells. A one-way analysis of variance was used for comparison of the means of continuous data between multiple groups， and the SNK-q test was used for comparison between two groups. Results Compared with the patients with liver cirrhosis， the patients with liver cancer had a significantly higher concentration of LPA in plasma （4.99±0.55 μmol/L vs 2.63±0.43 μmol/L， P<0.05） and peritoneal effusion （5.19±0.63 μmol/L vs 2.91±0.46 μmol/L， P<0.05）， and the patients with liver cancer also had a significantly higher level of plasma LPA than the normal population （4.99±0.55 μmol/L vs 1.61±0.39 μmol/L， P<0.05）. The cell proliferation assay showed that LPA significantly promoted the proliferation of SMMC7721 cells， and cell proliferation rate increased with the increase in dose and time； in particular， the middle-and high-dose groups had a significantly higher proliferation rate than the control group （P<0.05）. PTX inhibited the proliferative capacity of SMMC7721 cells in a time-dependent manner， and there was a significant difference between the groups （P<0.05）. The proliferation rate of the 72-hour high-dose LPA group was 3.6 times that of the control group， while the proliferation rate of the PTX group was 0.6 times that of the control group； the proliferation rate of the 72-hour high-dose LPA+PTX group was 1.2 times that of the control group. In addition， LPA increased the migration ability of hepatoma cells， while PTX inhibited their migration， in a time-dependent manner， and there was a significant difference between the groups （P<0.05）. The migration rate of the 72-hour high-dose LPA group was 3.09 times that of the control group， while the migration rate of the PTX group was 0.4 times that of the control group； the migration rate of the 72-hour high-dose LPA+PTX group was 0.99 times that of the control group. qPCR and Western blot showed that there were significant reductions in the mRNA and protein expression levels of P53 in SMMC7721 cells after LPA treatment， while there were significant increases in the mRNA and protein expression levels of FAK and RhoA； there was a significant difference between the LPA group and the control group （P<0.05）. Conclusion There is an abnormal increase in the expression of LPA in patients with liver cancer， and LPA can promote the proliferation of liver cancer cells and increase their migration ability. At the same time， LPA changes the expression levels of P53， FAK， and RhoA， which may be associated with the promotion of tumor development and progression by LPA.
- Liver Neoplasms,
- Lysophospholipids,
- Pertussis Toxin

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References(20)

References

[1]	LI X, RAMADORI P, PFISTER D, et al. The immunological and metabolic landscape in primary and metastatic liver cancer[J]. Nat Rev Cancer, 2021, 21( 9): 541- 557. DOI: 10.1038/s41568-021-00383-9.
[2]	XU Z, LIU Y, LIANG F. Clinical efficacy of Danshen Chuanxiongqin Injection and its effect on serum levels of LPA,Hcy and MCP-1 in patients with ischemic stroke[J]. J Changchun Univ Chin Med, 2021, 37( 1): 84- 87. DOI: 10.13463/j.cnki.cczyy.2021.01.023. 许卓, 刘洋, 梁赋. 丹参川芎嗪注射液治疗缺血性脑卒中患者临床疗效及对血清LPA、Hcy、MCP-1水平的影响[J]. 长春中医药大学学报, 2021, 37( 1): 84- 87. DOI: 10.13463/j.cnki.cczyy.2021.01.023.
[3]	AIELLO S, CASIRAGHI F. Lysophosphatidic acid: Promoter of cancer progression and of tumor microenvironment development. A promising target for anticancer therapies?[J]. Cells, 2021, 10( 6): 1390. DOI: 10.3390/cells10061390.
[4]	RAY R, JANGDE N, SINGH SK, et al. Lysophosphatidic acid-RAGE axis promotes lung and mammary oncogenesis via protein kinase B and regulating tumor microenvironment[J]. Cell Commun Signal, 2020, 18( 1): 170. DOI: 10.1186/s12964-020-00666-y.
[5]	AMARAL RF, GERALDO LHM, EINICKER-LAMAS M, et al. Microglial lysophosphatidic acid promotes glioblastoma proliferation and migration via LPA₁ receptor[J]. J Neurochem, 2021, 156( 4): 499- 512. DOI: 10.1111/jnc.15097.
[6]	KLYMENKO Y, BOS B, CAMPBELL L, et al. Lysophosphatidic acid modulates ovarian cancer multicellular aggregate assembly and metastatic dissemination[J]. Sci Rep, 2020, 10( 1): 10877. DOI: 10.1038/s41598-020-67565-7.
[7]	GNOCCHI D, CAVALLUZZI MM, MANGIATORDI GF, et al. Xanthenylacetic acid derivatives effectively target lysophosphatidic acid receptor 6 to inhibit hepatocellular carcinoma cell growth[J]. ChemMedChem, 2021, 16( 13): 2121- 2129. DOI: 10.1002/cmdc.202100032.
[8]	DEHGHAN M, SHAHBAZI S, SALEHNIA M. Effect of lysophosphatidic acid on the vascular endothelial growth factor expression in autotransplanted mouse ovaries encapsulated in sodium alginate[J]. J Family Reprod Health, 2021, 15( 2): 91- 98. DOI: 10.18502/jfrh.v15i2.6449.
[9]	XIE Y, WANG XC, WU XW, et al. Lysophosphatidic acid receptor 4 regulates osteogenic and adipogenic differentiation of progenitor cells via inactivation of RhoA/ROCK1/β-catenin signaling[J]. Stem Cells, 2020, 38( 3): 451- 463. DOI: 10.1002/stem.3128.
[10]	MINAMI K, UEDA N, ISHIMOTO K, et al. Cooperation of G12/13 and Gi proteins via lysophosphatidic acid receptor-2(LPA₂) signaling enhances cancer cell survival to cisplatin[J]. Biochem Biophys Res Commun, 2020, 532( 3): 427- 432. DOI: 10.1016/j.bbrc.2020.08.087.
[11]	LEE SC, LIN KH, BALOGH A, et al. Dysregulation of lysophospholipid signaling by p53 in malignant cells and the tumor microenvironment[J]. Cell Signal, 2021, 78: 109850. DOI: 10.1016/j.cellsig.2020.109850.
[12]	ZHANG YZ, SHI HB, CHEN Y. Biological functions of apoptosis stimulating protein of p53 2 and its role in liver diseases[J]. J Clin Hepatol, 2018, 34( 11): 2443- 2447. DOI: 10.3969/j.issn.1001-5256.2018.11.039. 张译之, 时红波, 陈煜. p53凋亡刺激蛋白2的生物学功能及其在肝病中的作用[J]. 临床肝胆病杂志, 2018, 34( 11): 2443- 2447. DOI: 10.3969/j.issn.1001-5256.2018.11.039.
[13]	HUANG CC, TSENG TT, LIU SC, et al. S1P increases VEGF production in osteoblasts and facilitates endothelial progenitor cell angiogenesis by inhibiting miR-16-5p expression via the c-src/FAK signaling pathway in rheumatoid arthritis[J]. Cells, 2021, 10( 8): 2168. DOI: 10.3390/cells10082168.
[14]	WEI YH, WANG YF, LIU NB, et al. A FAK inhibitor boosts anti-PD1 immunotherapy in a hepatocellular carcinoma mouse model[J]. Front Pharmacol, 2022, 12: 820446. DOI: 10.3389/fphar.2021.820446.
[15]	LIAO Y, LIU L, YANG JY, et al. ATX/LPA axis regulates FAK activation, cell proliferation, apoptosis, and motility in human pancreatic cancer cells[J]. Vitro Cell Dev Biol Anim, 2022, 58( 4): 307- 315. DOI: 10.1007/s11626-022-00660-3.
[16]	SUMITOMO A, SIRIWACH R, THUMKEO D, et al. LPA induces keratinocyte differentiation and promotes skin barrier function through the LPAR1/LPAR5-RHO-ROCK-SRF axis[J]. J Invest Dermatol, 2019, 139( 5): 1010- 1022. DOI: 10.1016/j.jid.2018.10.034.
[17]	KIM D, KIM HJ, BAEK JO, et al. Lysophosphatidic acid mediates imiquimod-induced psoriasis-like symptoms by promoting keratinocyte proliferation through LPAR1/ROCK2/PI3K/AKT signaling pathway[J]. Int J Mol Sci, 2021, 22( 19): 10777. DOI: 10.3390/ijms221910777.
[18]	NAKAJIMA K, OKA S, TANIKAWA T, et al. Lysophosphatidylinositol induced morphological changes and stress fiber formation through the GPR55-RhoA-ROCK pathway[J]. Int J Mol Sci, 2022, 23( 18): 10932. DOI: 10.3390/ijms231810932.
[19]	INABA A, HARADA H, IKEZAKI S, et al. LPA₆-RhoA signals regulate junctional complexes for polarity and morphology establishment of maturation stage ameloblasts[J]. J Oral Biosci, 2022, 64( 1): 85- 92. DOI: 10.1016/j.job.2022.01.004.
[20]	BUTERA A, ROY M, ZAMPIERI C, et al. p53-driven lipidome influences non-cell-autonomous lysophospholipids in pancreatic cancer[J]. Biol Direct, 2022, 17( 1): 6. DOI: 10.1186/s13062-022-00319-9.

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Effect of lysophosphatidic acid on hepatoma cells and related mechanism

DOI: 10.3969/j.issn.1001-5256.2023.11.016