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Insufficient radiofrequency ablation promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells through Akt and ERK signaling pathways.

Dong S, Kong J, Kong F, Kong J, Gao J, Ke S, Wang S, Ding X, Sun W, Zheng L - J Transl Med (2013)

Bottom Line: Molecular changes of EMT were observed in SMMC7721-H and Huh7-H cells.LY294002 and PD98059 inhibited the EMT of SMMC7721-H and Huh7-H cells.Insufficient RFA may promote the EMT of HCC cells through Akt and ERK signaling pathways.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100043, China. wb.sun@yahoo.com.cn.

ABSTRACT

Background: Residual tumor progression after insufficient radiofrequency ablation (RFA) has been recently reported. However, whether epithelial-mesenchymal transition (EMT), which is a key process that drives cancer metastasis, is involved in the tumor progression after insufficient RFA is not well understood.

Methods: Human hepatocellular carcinoma (HCC) cell lines SMMC7721 and Huh7 were used. Insufficient RFA was simulated using a water bath (47°C 5 min, 10 min, 15 min, 20 min and 25 min gradually). MTT assay was used to evaluate the proliferation of HCC cells in vitro. Migration and invasion of HCC cells were determined by transwell assay. The molecular changes in HCC cells after insufficient RFA were evaluated by western blot. LY294002 and PD98059 were used to treat HCC cells. An ectopic nude mice model and a tail vein metastatic assay were used to evaluate the growth and metastatic potential of SMMC7721 cells in vivo after insufficient RFA.

Results: SMMC7721 and Huh7 cells after insufficient RFA (named as SMMC7721-H and Huh7-H respectively) exhibited enhanced proliferation, migration and invasion (6.4% and 23.6%, 33.2% and 66.1%, and 44.1% and 57.4% increase respectively) in vitro. Molecular changes of EMT were observed in SMMC7721-H and Huh7-H cells. LY294002 and PD98059 inhibited the EMT of SMMC7721-H and Huh7-H cells. SMMC7721-H cells also exhibited larger tumor size (1440.8±250.3 mm3 versus 1048.56±227.6 mm3) and more lung metastasis (97.4% increase) than SMMC7721 cells in vivo. Higher expression of PCNA, N-cadherin and MMP-2 and MMP-9, was also observed in SMMC7721-H tumors.

Conclusions: Insufficient RFA could directly promote the invasiveness and metastasis of HCC cells. Insufficient RFA may promote the EMT of HCC cells through Akt and ERK signaling pathways.

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HCC cells after insufficient RFA exhibited enhanced metastatic ability in vivo. SMMC7721 and SMMC7721-H cells were injected through tail vein of mice. (A) Lung metastasis was assessed. (B) The lung tissues were sectioned serially and stained with HE. Representative images of HE were shown (× 200). (C) The numbers of metastatic tumors were counted. Error bars represent the SEM of data obtained in three independent experiments. P value <0.05 was considered statistically significant; ***p < 0.001.
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Figure 5: HCC cells after insufficient RFA exhibited enhanced metastatic ability in vivo. SMMC7721 and SMMC7721-H cells were injected through tail vein of mice. (A) Lung metastasis was assessed. (B) The lung tissues were sectioned serially and stained with HE. Representative images of HE were shown (× 200). (C) The numbers of metastatic tumors were counted. Error bars represent the SEM of data obtained in three independent experiments. P value <0.05 was considered statistically significant; ***p < 0.001.

Mentions: To determine the effects of insufficient RFA on the in vivo metastasis of SMMC7721 cells, a tail vein metastasis assay was used. The extent of the metastatic tumors on the surface of the lung was significantly increased (97.4% increase) in mice receiving SMMC7721-H cells compared with SMMC7721 cells (Figure 5A). The lung tissues were sectioned serially and HE staining also confirmed the results above (Figure 5B and C). However, there were no apparent changes in body weight in the mice (Additional file2B).


Insufficient radiofrequency ablation promotes epithelial-mesenchymal transition of hepatocellular carcinoma cells through Akt and ERK signaling pathways.

Dong S, Kong J, Kong F, Kong J, Gao J, Ke S, Wang S, Ding X, Sun W, Zheng L - J Transl Med (2013)

HCC cells after insufficient RFA exhibited enhanced metastatic ability in vivo. SMMC7721 and SMMC7721-H cells were injected through tail vein of mice. (A) Lung metastasis was assessed. (B) The lung tissues were sectioned serially and stained with HE. Representative images of HE were shown (× 200). (C) The numbers of metastatic tumors were counted. Error bars represent the SEM of data obtained in three independent experiments. P value <0.05 was considered statistically significant; ***p < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3842745&req=5

Figure 5: HCC cells after insufficient RFA exhibited enhanced metastatic ability in vivo. SMMC7721 and SMMC7721-H cells were injected through tail vein of mice. (A) Lung metastasis was assessed. (B) The lung tissues were sectioned serially and stained with HE. Representative images of HE were shown (× 200). (C) The numbers of metastatic tumors were counted. Error bars represent the SEM of data obtained in three independent experiments. P value <0.05 was considered statistically significant; ***p < 0.001.
Mentions: To determine the effects of insufficient RFA on the in vivo metastasis of SMMC7721 cells, a tail vein metastasis assay was used. The extent of the metastatic tumors on the surface of the lung was significantly increased (97.4% increase) in mice receiving SMMC7721-H cells compared with SMMC7721 cells (Figure 5A). The lung tissues were sectioned serially and HE staining also confirmed the results above (Figure 5B and C). However, there were no apparent changes in body weight in the mice (Additional file2B).

Bottom Line: Molecular changes of EMT were observed in SMMC7721-H and Huh7-H cells.LY294002 and PD98059 inhibited the EMT of SMMC7721-H and Huh7-H cells.Insufficient RFA may promote the EMT of HCC cells through Akt and ERK signaling pathways.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, 100043, China. wb.sun@yahoo.com.cn.

ABSTRACT

Background: Residual tumor progression after insufficient radiofrequency ablation (RFA) has been recently reported. However, whether epithelial-mesenchymal transition (EMT), which is a key process that drives cancer metastasis, is involved in the tumor progression after insufficient RFA is not well understood.

Methods: Human hepatocellular carcinoma (HCC) cell lines SMMC7721 and Huh7 were used. Insufficient RFA was simulated using a water bath (47°C 5 min, 10 min, 15 min, 20 min and 25 min gradually). MTT assay was used to evaluate the proliferation of HCC cells in vitro. Migration and invasion of HCC cells were determined by transwell assay. The molecular changes in HCC cells after insufficient RFA were evaluated by western blot. LY294002 and PD98059 were used to treat HCC cells. An ectopic nude mice model and a tail vein metastatic assay were used to evaluate the growth and metastatic potential of SMMC7721 cells in vivo after insufficient RFA.

Results: SMMC7721 and Huh7 cells after insufficient RFA (named as SMMC7721-H and Huh7-H respectively) exhibited enhanced proliferation, migration and invasion (6.4% and 23.6%, 33.2% and 66.1%, and 44.1% and 57.4% increase respectively) in vitro. Molecular changes of EMT were observed in SMMC7721-H and Huh7-H cells. LY294002 and PD98059 inhibited the EMT of SMMC7721-H and Huh7-H cells. SMMC7721-H cells also exhibited larger tumor size (1440.8±250.3 mm3 versus 1048.56±227.6 mm3) and more lung metastasis (97.4% increase) than SMMC7721 cells in vivo. Higher expression of PCNA, N-cadherin and MMP-2 and MMP-9, was also observed in SMMC7721-H tumors.

Conclusions: Insufficient RFA could directly promote the invasiveness and metastasis of HCC cells. Insufficient RFA may promote the EMT of HCC cells through Akt and ERK signaling pathways.

Show MeSH
Related in: MedlinePlus