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Methylation of CHFR sensitizes esophageal squamous cell cancer to docetaxel and paclitaxel.

Yun T, Liu Y, Gao D, Linghu E, Brock MV, Yin D, Zhan Q, Herman JG, Guo M - Genes Cancer (2015)

Bottom Line: CHFR methylation has been found frequently in different cancers and is regarded as a marker of taxane sensitivity.No difference was found with either cisplatin or VP16 treatment in either group (p>0.05).In CHFR methylated cells, treatment with docetaxel or paclitaxel resulted in almost all cells being suspended in G0/G1 phase of the cell cycle.

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.

ABSTRACT
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide. Both genetic and epigenetic changes are involved in esophageal carcinogenesis. CHFR methylation has been found frequently in different cancers and is regarded as a marker of taxane sensitivity. CHFR methylation was found in 0% (0/16) of normal mucosa, 2.9% (1/34) of grade I dysplasia, 0% (0/8) of grade II dysplasia, 12.5% (1/8) of grade III dysplasia and 45% (49/109) of invasive cancer. When treated with docetaxel or paclitaxel, cell viability was lower in CHFR methylated esophageal cancer cells than in unmethylated cells (p<0.05). No difference was found with either cisplatin or VP16 treatment in either group (p>0.05). In CHFR methylated cells, treatment with docetaxel or paclitaxel resulted in almost all cells being suspended in G0/G1 phase of the cell cycle. After 5-AZ treatment, there was an increased fraction of CHFR-methylated cells in S and G2/M phases (p<0.05). In conclusion, CHFR is frequently methylated in ESCC and the expression of CHFR is regulated by promoter region methylation. CHFR methylation is a late stage event in ESCC. Methylation of CHFR sensitized ESCC cells to taxanes. 5-AZ may re-sensitize chemotherapy resistant in refractory tumors by inducing cell cycle phase re-distribution.

No MeSH data available.


Related in: MedlinePlus

Cell viability in CHFR methylated (M) and unmethylated (U) esophageal cancer cellsThe viability of CHFR methylated (KYSE70, KYSE150) and unmethylated (KYSE140, KYSE450) cell lines treated by VP16, cisplatin, paclitaxel or docetaxel, with or without 5-AZ treatment at 24hrs, 48hrs or 72hrs as shown in Table 2.
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Figure 2: Cell viability in CHFR methylated (M) and unmethylated (U) esophageal cancer cellsThe viability of CHFR methylated (KYSE70, KYSE150) and unmethylated (KYSE140, KYSE450) cell lines treated by VP16, cisplatin, paclitaxel or docetaxel, with or without 5-AZ treatment at 24hrs, 48hrs or 72hrs as shown in Table 2.

Mentions: Methylation of CHFR has been shown to sensitize different cancers to taxane treatment [24-26]. In a small study, no association was found between CHFR methylation and the sensitivity of esophageal cancer to cisplatin and 5-fluorouracil [22]. In this study, we compared the methylation status of CHFR and the sensitivity of esophageal cancer cells to paclitaxel, docetaxel, VP16 and cisplatin. No significant difference was found between the viability of unmethylated cells (KYSE140, KYSE450) and methylated cells (KYSE70, KYSE150) in cisplatin or VP16 treatment group (Figure2, table2, all p>0.05). Methylated cells (KYSE70, KYSE150) were significantly more likely to undergo apoptosis than unmethylated cells (KYSE140, KYSE450) after paclitaxel or docetaxel treatment (Figure2, table 2, all p< 0.05). The sensitivity of these CHFR methylated cells was further evaluated with or without 5-AZ treatment. In the cisplatin or VP16 treatment group, cell viability was unchanged with or without 5-AZ treatment (Figure2, table2, all p>0.05). While in the paclitaxel and docetaxel treated groups, no significant difference was found between the methylated (KYSE70, KYSE150) and unmethylated cells (KYSE140, KYSE450) when treated with 5-AZ (Figure2, table2, all p>0.05). These results further suggest that the methylation of CHFR sensitizes esophageal cancer cells to paclitaxel and docetaxel, while the restoration of CHFR expression with 5-AZ induces resistance to these chemotherapeutic agents.


Methylation of CHFR sensitizes esophageal squamous cell cancer to docetaxel and paclitaxel.

Yun T, Liu Y, Gao D, Linghu E, Brock MV, Yin D, Zhan Q, Herman JG, Guo M - Genes Cancer (2015)

Cell viability in CHFR methylated (M) and unmethylated (U) esophageal cancer cellsThe viability of CHFR methylated (KYSE70, KYSE150) and unmethylated (KYSE140, KYSE450) cell lines treated by VP16, cisplatin, paclitaxel or docetaxel, with or without 5-AZ treatment at 24hrs, 48hrs or 72hrs as shown in Table 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4362483&req=5

Figure 2: Cell viability in CHFR methylated (M) and unmethylated (U) esophageal cancer cellsThe viability of CHFR methylated (KYSE70, KYSE150) and unmethylated (KYSE140, KYSE450) cell lines treated by VP16, cisplatin, paclitaxel or docetaxel, with or without 5-AZ treatment at 24hrs, 48hrs or 72hrs as shown in Table 2.
Mentions: Methylation of CHFR has been shown to sensitize different cancers to taxane treatment [24-26]. In a small study, no association was found between CHFR methylation and the sensitivity of esophageal cancer to cisplatin and 5-fluorouracil [22]. In this study, we compared the methylation status of CHFR and the sensitivity of esophageal cancer cells to paclitaxel, docetaxel, VP16 and cisplatin. No significant difference was found between the viability of unmethylated cells (KYSE140, KYSE450) and methylated cells (KYSE70, KYSE150) in cisplatin or VP16 treatment group (Figure2, table2, all p>0.05). Methylated cells (KYSE70, KYSE150) were significantly more likely to undergo apoptosis than unmethylated cells (KYSE140, KYSE450) after paclitaxel or docetaxel treatment (Figure2, table 2, all p< 0.05). The sensitivity of these CHFR methylated cells was further evaluated with or without 5-AZ treatment. In the cisplatin or VP16 treatment group, cell viability was unchanged with or without 5-AZ treatment (Figure2, table2, all p>0.05). While in the paclitaxel and docetaxel treated groups, no significant difference was found between the methylated (KYSE70, KYSE150) and unmethylated cells (KYSE140, KYSE450) when treated with 5-AZ (Figure2, table2, all p>0.05). These results further suggest that the methylation of CHFR sensitizes esophageal cancer cells to paclitaxel and docetaxel, while the restoration of CHFR expression with 5-AZ induces resistance to these chemotherapeutic agents.

Bottom Line: CHFR methylation has been found frequently in different cancers and is regarded as a marker of taxane sensitivity.No difference was found with either cisplatin or VP16 treatment in either group (p>0.05).In CHFR methylated cells, treatment with docetaxel or paclitaxel resulted in almost all cells being suspended in G0/G1 phase of the cell cycle.

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.

ABSTRACT
Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide. Both genetic and epigenetic changes are involved in esophageal carcinogenesis. CHFR methylation has been found frequently in different cancers and is regarded as a marker of taxane sensitivity. CHFR methylation was found in 0% (0/16) of normal mucosa, 2.9% (1/34) of grade I dysplasia, 0% (0/8) of grade II dysplasia, 12.5% (1/8) of grade III dysplasia and 45% (49/109) of invasive cancer. When treated with docetaxel or paclitaxel, cell viability was lower in CHFR methylated esophageal cancer cells than in unmethylated cells (p<0.05). No difference was found with either cisplatin or VP16 treatment in either group (p>0.05). In CHFR methylated cells, treatment with docetaxel or paclitaxel resulted in almost all cells being suspended in G0/G1 phase of the cell cycle. After 5-AZ treatment, there was an increased fraction of CHFR-methylated cells in S and G2/M phases (p<0.05). In conclusion, CHFR is frequently methylated in ESCC and the expression of CHFR is regulated by promoter region methylation. CHFR methylation is a late stage event in ESCC. Methylation of CHFR sensitized ESCC cells to taxanes. 5-AZ may re-sensitize chemotherapy resistant in refractory tumors by inducing cell cycle phase re-distribution.

No MeSH data available.


Related in: MedlinePlus