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Overexpression of lactate dehydrogenase-A in human intrahepatic cholangiocarcinoma: its implication for treatment.

Yu Y, Liao M, Liu R, Chen J, Feng H, Fu Z - World J Surg Oncol (2014)

Bottom Line: Previous studies have shown that lactate dehydrogenase-A (LDH-A) is strongly expressed in several malignancies, that LDH-A expression is associated with poor prognosis, and that LDH-A inhibition severely diminishes tumorigenicity.Reduction of LDH-A by RNA interference (RNAi) inhibited cell growth and induced apoptosis in HuCCT-1 cells.This result correlated with the elevation of cytoplasmic reactive oxygen species (ROS) levels.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Minimally Invasive Surgery, Department of General Surgery, First Affiliated Hospital of Nanjing Medical University, NO, 300, Guangzhou Road, Nanjing 210029, China. fuzan2011@163.com.

ABSTRACT

Background: Previous studies have shown that lactate dehydrogenase-A (LDH-A) is strongly expressed in several malignancies, that LDH-A expression is associated with poor prognosis, and that LDH-A inhibition severely diminishes tumorigenicity. However, little is known about the implications of LDH-A expression in intrahepatic cholangiocarcinoma. The purpose of this study was to investigate the expression of LDH-A and to clarify its effect on intrahepatic cholangiocarcinoma.

Methods: We studied the expression of LDH-A in tissue samples from patients with intrahepatic cholangiocarcinoma (n = 54) using the ultrasensitive surfactant protein (S-P) immunohistochemical method. We then inhibited LDH-A using small hairpin RNA (shRNA) in the cholangiocarcinoma cell line HuCCT-1 in vitro to study the role it plays in promoting growth and escaping apoptosis.

Results: We report that LDH-A was overexpressed in 52 of 54 (96%) paraffin-embedded cancer tissue samples and 0 of 54 para-carcinoma tissue samples. Reduction of LDH-A by RNA interference (RNAi) inhibited cell growth and induced apoptosis in HuCCT-1 cells. This result correlated with the elevation of cytoplasmic reactive oxygen species (ROS) levels.

Conclusions: LDH-A expression is closely correlated with histopathological variables of intrahepatic cholangiocarcinoma, indicating that LDH-A may serve as a new treatment target.

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Related in: MedlinePlus

Intracellular ROS production was detected with DCFDA fluorescence and monitored by flow cytometry at 72 hours post-transfection with shLDH-A (RNAi) or siControl (NC). DCFDA, dichlorofluorescin diacetate; RNAi, RNA interference; ROS, reactive oxygen species; sh, short hairpin.
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Figure 5: Intracellular ROS production was detected with DCFDA fluorescence and monitored by flow cytometry at 72 hours post-transfection with shLDH-A (RNAi) or siControl (NC). DCFDA, dichlorofluorescin diacetate; RNAi, RNA interference; ROS, reactive oxygen species; sh, short hairpin.

Mentions: Silencing LDH-A has been reported to increase the OXPHOS capacity and to induce oxidative stress [6,14]. Therefore, we hypothesized that ROS, generated during respiration [16], might increase following a reduction in the expression of LDH-A in cholangiocarcinoma. ROS levels in the RNAi groups were three times higher than those in the NC group (Figure 5). These data suggest that LDH-A expression is linked to the ROS level of ICC and that inhibition of LDH-A increases ROS levels.


Overexpression of lactate dehydrogenase-A in human intrahepatic cholangiocarcinoma: its implication for treatment.

Yu Y, Liao M, Liu R, Chen J, Feng H, Fu Z - World J Surg Oncol (2014)

Intracellular ROS production was detected with DCFDA fluorescence and monitored by flow cytometry at 72 hours post-transfection with shLDH-A (RNAi) or siControl (NC). DCFDA, dichlorofluorescin diacetate; RNAi, RNA interference; ROS, reactive oxygen species; sh, short hairpin.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4230420&req=5

Figure 5: Intracellular ROS production was detected with DCFDA fluorescence and monitored by flow cytometry at 72 hours post-transfection with shLDH-A (RNAi) or siControl (NC). DCFDA, dichlorofluorescin diacetate; RNAi, RNA interference; ROS, reactive oxygen species; sh, short hairpin.
Mentions: Silencing LDH-A has been reported to increase the OXPHOS capacity and to induce oxidative stress [6,14]. Therefore, we hypothesized that ROS, generated during respiration [16], might increase following a reduction in the expression of LDH-A in cholangiocarcinoma. ROS levels in the RNAi groups were three times higher than those in the NC group (Figure 5). These data suggest that LDH-A expression is linked to the ROS level of ICC and that inhibition of LDH-A increases ROS levels.

Bottom Line: Previous studies have shown that lactate dehydrogenase-A (LDH-A) is strongly expressed in several malignancies, that LDH-A expression is associated with poor prognosis, and that LDH-A inhibition severely diminishes tumorigenicity.Reduction of LDH-A by RNA interference (RNAi) inhibited cell growth and induced apoptosis in HuCCT-1 cells.This result correlated with the elevation of cytoplasmic reactive oxygen species (ROS) levels.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Minimally Invasive Surgery, Department of General Surgery, First Affiliated Hospital of Nanjing Medical University, NO, 300, Guangzhou Road, Nanjing 210029, China. fuzan2011@163.com.

ABSTRACT

Background: Previous studies have shown that lactate dehydrogenase-A (LDH-A) is strongly expressed in several malignancies, that LDH-A expression is associated with poor prognosis, and that LDH-A inhibition severely diminishes tumorigenicity. However, little is known about the implications of LDH-A expression in intrahepatic cholangiocarcinoma. The purpose of this study was to investigate the expression of LDH-A and to clarify its effect on intrahepatic cholangiocarcinoma.

Methods: We studied the expression of LDH-A in tissue samples from patients with intrahepatic cholangiocarcinoma (n = 54) using the ultrasensitive surfactant protein (S-P) immunohistochemical method. We then inhibited LDH-A using small hairpin RNA (shRNA) in the cholangiocarcinoma cell line HuCCT-1 in vitro to study the role it plays in promoting growth and escaping apoptosis.

Results: We report that LDH-A was overexpressed in 52 of 54 (96%) paraffin-embedded cancer tissue samples and 0 of 54 para-carcinoma tissue samples. Reduction of LDH-A by RNA interference (RNAi) inhibited cell growth and induced apoptosis in HuCCT-1 cells. This result correlated with the elevation of cytoplasmic reactive oxygen species (ROS) levels.

Conclusions: LDH-A expression is closely correlated with histopathological variables of intrahepatic cholangiocarcinoma, indicating that LDH-A may serve as a new treatment target.

Show MeSH
Related in: MedlinePlus