PMID- 34913065
OWN - NLM
STAT- MEDLINE
DCOM- 20220309
LR  - 20220309
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 25
IP  - 2
DP  - 2022 Feb
TI  - Kangxianruangan granule‑containing serum mediated inhibition of hepatic oval cell 
      differentiation into hepatocellular carcinoma cells via the Wnt‑1/beta‑catenin 
      signaling pathway.
LID - 55 [pii]
LID - 10.3892/mmr.2021.12571 [doi]
AB  - Hepatocellular carcinoma is a malignancy with poor clinical prognosis. Hepatic 
      oval cells (HOCs) tend to differentiate into cancerous hepatocellular carcinoma 
      cells (HCCs) in the tumor microenvironment. The purpose of the present study was 
      to explore the role of kangxianruangan granule (KXRG)‑containing serum in 
      inhibiting the differentiation of HOCs into HCCs via the Wnt‑1/beta‑catenin 
      signaling pathway. N‑methyl‑N'‑nitro‑N‑nitrosoguanidine (MNNG) was applied to 
      induce the transformation of the rat HOC cell line WB‑F344 into HCCs. The 
      overexpression plasmid, Wnt‑1‑up, was utilized to increase Wnt‑1 expression. 
      Subsequently, high, medium and low concentrations of KXRG were applied to 
      MNNG‑treated WB‑F344 cells to assess the inhibitory effect of KXRG on cell 
      differentiation. Flow cytometry was conducted to detect the cell cycle 
      distribution, apoptotic rate and expression of cytokeratin‑19 (CK‑19) protein in 
      cells. An immunofluorescence double staining protocol was used to detect the 
      expression of Wnt‑1 and beta‑catenin. ELISAs were performed to detect alpha fetoprotein 
      in the cell supernatants. Reverse transcription‑quantitative PCR and western 
      blotting were conducted to detect the mRNA and protein expression levels of 
      Wnt‑1, beta‑catenin, Cyclin D1, C‑myc, matrix metalloproteinase‑7 (MMP‑7), Axin2 and 
      epithelial cell adhesion molecule (EpCAM) in cells. Compared with the normal 
      group, the apoptotic rate, proportion of S phase cells, concentration of AFP in 
      the cell supernatant, level of CK‑19 protein, and mRNA and protein expression 
      levels of Wnt‑1, beta‑catenin, Cyclin D1, C‑myc, MMP‑7, Axin2 and EpCAM were all 
      significantly increased in the model group. Addition of KXRG significantly 
      reduced the aforementioned indicators compared with the model group. Moreover, 
      Wnt‑1 overexpression further increased the aforementioned indicators compared 
      with the model group, whereas KXRG significantly inhibited these effects. The 
      results indicated that KXRG inhibited the differentiation of HOCs into HCCs via 
      the Wnt‑1/beta‑catenin signaling pathway, which suggested the potential clinical 
      application of KXRG for the prevention of hepatocellular carcinoma.
FAU - Tang, Wenqian
AU  - Tang W
AD  - Health Management Centre, Hubei Provincial Hospital of Traditional Chinese 
      Medicine, Wuhan, Hubei 430074, P.R. China.
FAU - Xue, Juan
AU  - Xue J
AD  - Clinical College of Chinese Medicine, Hubei University of Chinese Medicine, 
      Wuhan, Hubei 430061, P.R. China.
FAU - Luo, Lei
AU  - Luo L
AD  - Health Management Centre, Hubei Provincial Hospital of Traditional Chinese 
      Medicine, Wuhan, Hubei 430074, P.R. China.
FAU - Wang, Yao
AU  - Wang Y
AD  - Department of Infectious Diseases, Renmin Hospital of Wuhan University, Wuhan, 
      Hubei 430060, P.R. China.
FAU - Cai, Xin
AU  - Cai X
AD  - Department of Infectious Diseases, The People's Hospital of Jiangshan, Jiangshan, 
      Zhejiang 324100, P.R. China.
FAU - Liu, Yuqing
AU  - Liu Y
AD  - Department of Infectious Diseases, Yancheng TCM Hospital Affiliated Nanjing 
      University of Chinese Medicine, Nanjing, Jiangsu 224001, P.R. China.
FAU - Huang, Dawei
AU  - Huang D
AD  - Department of Hepatology, Hubei Provincial Hospital of Traditional Chinese 
      Medicine, Wuhan, Hubei 430074, P.R. China.
FAU - Wang, Xiaodong
AU  - Wang X
AD  - Department of Hepatology, Hubei Provincial Hospital of Traditional Chinese 
      Medicine, Wuhan, Hubei 430074, P.R. China.
FAU - He, Tangqing
AU  - He T
AD  - Department of Hepatology, Hubei Provincial Hospital of Traditional Chinese 
      Medicine, Wuhan, Hubei 430074, P.R. China.
FAU - Lu, Dingbo
AU  - Lu D
AD  - Department of Hepatology, Hubei Provincial Hospital of Traditional Chinese 
      Medicine, Wuhan, Hubei 430074, P.R. China.
FAU - Yang, Fan
AU  - Yang F
AD  - Health Management Centre, Hubei Provincial Hospital of Traditional Chinese 
      Medicine, Wuhan, Hubei 430074, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20211216
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Drugs, Chinese Herbal)
RN  - 0 (kangxian ruangan)
RN  - 12H3O2UGSF (Methylnitronitrosoguanidine)
SB  - IM
MH  - Animals
MH  - Carcinoma, Hepatocellular/chemically induced/pathology/*prevention & control
MH  - Cell Differentiation/drug effects
MH  - Cell Line, Tumor
MH  - Cell Transformation, Neoplastic/chemically induced/*drug effects/pathology
MH  - Disease Models, Animal
MH  - Drugs, Chinese Herbal/*administration & dosage
MH  - Humans
MH  - Liver/cytology/pathology
MH  - Liver Neoplasms, Experimental/chemically induced/pathology/*prevention & control
MH  - Male
MH  - Methylnitronitrosoguanidine/toxicity
MH  - Rats
MH  - Tumor Microenvironment/drug effects
MH  - Wnt Signaling Pathway/*drug effects
PMC - PMC8711029
OTO - NOTNLM
OT  - Wnt‑1/beta‑catenin signaling pathway
OT  - hepatic oval cells
OT  - hepatocellular carcinoma cells
OT  - kangxianruangan granule‑containing serum
COIS- The authors declare that they have no competing interests.
EDAT- 2021/12/17 06:00
MHDA- 2022/03/11 06:00
PMCR- 2021/12/15
CRDT- 2021/12/16 06:40
PHST- 2020/11/05 00:00 [received]
PHST- 2021/04/27 00:00 [accepted]
PHST- 2021/12/16 06:40 [entrez]
PHST- 2021/12/17 06:00 [pubmed]
PHST- 2022/03/11 06:00 [medline]
PHST- 2021/12/15 00:00 [pmc-release]
AID - 55 [pii]
AID - MMR-0-0-12571 [pii]
AID - 10.3892/mmr.2021.12571 [doi]
PST - ppublish
SO  - Mol Med Rep. 2022 Feb;25(2):55. doi: 10.3892/mmr.2021.12571. Epub 2021 Dec 16.