Limits...
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.

Show MeSH

Related in: MedlinePlus

Immunohistochemical staining of lactate dehydrogenase-5 (LDH-A) in (A) para-carcinoma tissue and (B) tissue sections from human ICC. (B) Corresponding (original magnification, 200×). (A) Weak cytoplasmic and nuclear expression. (B) Strong cytoplasmic and nuclear expression. ICC, intrahepatic cholangiocarcinoma.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Immunohistochemical staining of lactate dehydrogenase-5 (LDH-A) in (A) para-carcinoma tissue and (B) tissue sections from human ICC. (B) Corresponding (original magnification, 200×). (A) Weak cytoplasmic and nuclear expression. (B) Strong cytoplasmic and nuclear expression. ICC, intrahepatic cholangiocarcinoma.

Mentions: First, we studied the expression of LDH-A in ICC tissue samples using the S-P immunohistochemical method. Immunohistochemical expression was observed to be nuclear and/or cytoplasmic (Figure 1). Of 42 ICC tissue samples, 23 (54.8%) demonstrated high LDH-A reactivity as categorized using the grading system previously mentioned [15]. In 16 ICC tissue samples, adjacent non-cancerous tissues were consistently unreactive to LDH-A. The association of LDH-A with histopathological variables is shown in Table 1. LDH-A expression was positively correlated with histopathological variables (P <0.05). That is, the overexpression of LDH-A was more prevalent in poorly differentiated ICC cells. However, no significant association was noted between LDH-A expression and lymph-node metastasis.


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)

Immunohistochemical staining of lactate dehydrogenase-5 (LDH-A) in (A) para-carcinoma tissue and (B) tissue sections from human ICC. (B) Corresponding (original magnification, 200×). (A) Weak cytoplasmic and nuclear expression. (B) Strong cytoplasmic and nuclear expression. ICC, intrahepatic cholangiocarcinoma.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Immunohistochemical staining of lactate dehydrogenase-5 (LDH-A) in (A) para-carcinoma tissue and (B) tissue sections from human ICC. (B) Corresponding (original magnification, 200×). (A) Weak cytoplasmic and nuclear expression. (B) Strong cytoplasmic and nuclear expression. ICC, intrahepatic cholangiocarcinoma.
Mentions: First, we studied the expression of LDH-A in ICC tissue samples using the S-P immunohistochemical method. Immunohistochemical expression was observed to be nuclear and/or cytoplasmic (Figure 1). Of 42 ICC tissue samples, 23 (54.8%) demonstrated high LDH-A reactivity as categorized using the grading system previously mentioned [15]. In 16 ICC tissue samples, adjacent non-cancerous tissues were consistently unreactive to LDH-A. The association of LDH-A with histopathological variables is shown in Table 1. LDH-A expression was positively correlated with histopathological variables (P <0.05). That is, the overexpression of LDH-A was more prevalent in poorly differentiated ICC cells. However, no significant association was noted between LDH-A expression and lymph-node metastasis.

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