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ISSN 1001-5256 (Print)
ISSN 2097-3497 (Online)
CN 22-1108/R
Volume 39 Issue 11
Nov.  2023
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Article Contents

Effect of lysophosphatidic acid on hepatoma cells and related mechanism

DOI: 10.3969/j.issn.1001-5256.2023.11.016
Research funding:

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

More Information
  • 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
  •   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.

     

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