2019 Fiscal Year Research-status Report
Periodontitis induced alterations of gut microbial metabolite promotes liver cancer through senescence
| Project/Area Number |
19K18963
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| Research Institution | Hiroshima University |
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Principal Investigator |
NGUYEN THAO 広島大学, 病院(医), 研究員 (40733837)
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Keywords | Gastroenterology / Cancer / Metabolism / Bile acids |
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| Outline of Annual Research Achievements |
We aimed to examine the effect of DCA on hepatic stellate cells (HSCs), and its subsequent indirect effect on liver cancer cells. LX2 cells, a human HSC line, were treated with DCA. This resulted in cellular senescence in LX2, then HCC cells were treated with conditioned media, that promoted cell migration and invasion together with epithelial mesenchymal transition. These changes were attenuated in the concomitant presence of neutralizing antibody against IL8 or TGFb. Pathological analysis of surgical specimen from HCC patients revealed that DCA and senescent HSCs were detected in the stroma surrounding HCC areas. Collectively, our data suggest an important role of HSC senescence for the malignant biological behaviors of HCC via induction of SASP factors, particularly IL8 and TGFb.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
I completed the in vitro part of the project, data and manuscript. I will submit to the journal in the near future.
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| Strategy for Future Research Activity |
a. Set up a system to examine the impact of oral S. noxia administration on tumorigenesis
Oral S.noxia D4 administration will be given to Mdr2/Abcb4-knockout (Mdr2-KO) mouse for 24 weeks. \
b. Investigate cellular senescence in HSCs
We will perform immunofluorescence analysis of liver section with desmin, alpha-SMA (to identify HSCs), and senescence markers (several SASP and b-galactosidase)
c. Examine the role of SASP in S. noxia-associated HCC development: We will deplete senescent HSCs from mice by an intravenous injection of liposomes carry small interfering RNA (siRNA) against HSP47
d. Explore whether antibiotics treatments reduce S.noxia-induced HCC by treating 4Abx of ampicillin, neomycin, metronidazole and vancomycin.
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| Causes of Carryover |
I plan to construct the interest genes, which are related to my project. So I plan to order the restrict enzymes for my purpose
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