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Association of ABCC2 and CDDP-Resistance in Two Sublines Resistant to CDDP Derived from a Human Nasopharyngeal Carcinoma Cell Line.

Xie SM, Fang WY, Liu TF, Yao KT, Zhong XY - J Oncol (2010)

Bottom Line: It was found that at the IC50 level, the resistance of CNE2-CDDP and CNE2-CDDP-5Fu against CDDP was 2.63-fold and 5.35-fold stronger than that of parental CNE2, respectively.Of the four ABC transporters (ABCB1, ABCC1, ABCC2 and ABCG2) related to MDR, only ABCC2 was found to be elevated both in CDDP-resistant sublines, with ABCC2 located in nucleus of CNE2-CDDP-5Fu but not in CNE2-CDDP and parental CNE2.Further research showed that compared to untreated CNE2, the intracellular levels of CDDP were decreased by 2.03-fold in CNE2-CDDP and 2.78-fold in CNE2-CDDP-5Fu.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research Institute, Southern Medical University, Guangzhou City, Guangdong Province 510515, China.

ABSTRACT
Cisplatin (CDDP) is one of the most active drugs to treat nasopharyngeal carcinoma (NPC) patients. To further understand the mechanisms of CDDP-resistance in NPC, two CDDP-resistant sublines (CNE2-CDDP and CNE2-CDDP-5Fu) derived from parental NPC cell line CNE2 were established. It was found that at the IC50 level, the resistance of CNE2-CDDP and CNE2-CDDP-5Fu against CDDP was 2.63-fold and 5.35-fold stronger than that of parental CNE2, respectively. Of the four ABC transporters (ABCB1, ABCC1, ABCC2 and ABCG2) related to MDR, only ABCC2 was found to be elevated both in CDDP-resistant sublines, with ABCC2 located in nucleus of CNE2-CDDP-5Fu but not in CNE2-CDDP and parental CNE2. Further research showed that compared to untreated CNE2, the intracellular levels of CDDP were decreased by 2.03-fold in CNE2-CDDP and 2.78-fold in CNE2-CDDP-5Fu. After treatment with PSC833, a modulator of MDR associated transporters including ABCC2, the intracellular level of CDDP was increased in CDDP-resistant sublines, and the resistance to CDDP was partially reversed from 2.63-fold to 1.62-fold in CNE2-CDDP and from 5.35-fold to 4.62-fold in CNE2-CDDP-5Fu. These data indicate that ABCC2 may play an important role in NPC resistant to CDDP.

No MeSH data available.


Related in: MedlinePlus

Immunocytochemical staining of ABCC2 expression in three cells (×200; SP method, DAB staining, and counterstaining with hematoxylin). (a) Blank control; (b) Parental cell line CNE2; (c) CDDP-resistant CNE2-CDDP cells; and (d) CDDP-5Fu-resistant CNE2-CDDP-5Fu cells. Black arrow: ABCC2 protein localized in cytoplasm; red arrow: ABCC2 protein localized in nucleus.
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fig2: Immunocytochemical staining of ABCC2 expression in three cells (×200; SP method, DAB staining, and counterstaining with hematoxylin). (a) Blank control; (b) Parental cell line CNE2; (c) CDDP-resistant CNE2-CDDP cells; and (d) CDDP-5Fu-resistant CNE2-CDDP-5Fu cells. Black arrow: ABCC2 protein localized in cytoplasm; red arrow: ABCC2 protein localized in nucleus.

Mentions: Since ABCC2 was found to be overexpressed both in CNE-CDDP and CNE2-CDDP-5Fu, and previous studies have shown that ABCC2 can be localized in the nuclear membrane of CDDP-resistant cells [22], immunocytochemistry staining method was used to detect the ABCC2 protein expression. As shown in Figure 2, ABCC2 protein was found to be localized in cytoplasm. The expression level of ABCC2 protein in CDDP-resistant sublines was stronger than that in parental CNE2. Interestingly, ABCC2 protein was also found to be localized in nucleus of CNE2-CDDP-5Fu cells.


Association of ABCC2 and CDDP-Resistance in Two Sublines Resistant to CDDP Derived from a Human Nasopharyngeal Carcinoma Cell Line.

Xie SM, Fang WY, Liu TF, Yao KT, Zhong XY - J Oncol (2010)

Immunocytochemical staining of ABCC2 expression in three cells (×200; SP method, DAB staining, and counterstaining with hematoxylin). (a) Blank control; (b) Parental cell line CNE2; (c) CDDP-resistant CNE2-CDDP cells; and (d) CDDP-5Fu-resistant CNE2-CDDP-5Fu cells. Black arrow: ABCC2 protein localized in cytoplasm; red arrow: ABCC2 protein localized in nucleus.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2902222&req=5

fig2: Immunocytochemical staining of ABCC2 expression in three cells (×200; SP method, DAB staining, and counterstaining with hematoxylin). (a) Blank control; (b) Parental cell line CNE2; (c) CDDP-resistant CNE2-CDDP cells; and (d) CDDP-5Fu-resistant CNE2-CDDP-5Fu cells. Black arrow: ABCC2 protein localized in cytoplasm; red arrow: ABCC2 protein localized in nucleus.
Mentions: Since ABCC2 was found to be overexpressed both in CNE-CDDP and CNE2-CDDP-5Fu, and previous studies have shown that ABCC2 can be localized in the nuclear membrane of CDDP-resistant cells [22], immunocytochemistry staining method was used to detect the ABCC2 protein expression. As shown in Figure 2, ABCC2 protein was found to be localized in cytoplasm. The expression level of ABCC2 protein in CDDP-resistant sublines was stronger than that in parental CNE2. Interestingly, ABCC2 protein was also found to be localized in nucleus of CNE2-CDDP-5Fu cells.

Bottom Line: It was found that at the IC50 level, the resistance of CNE2-CDDP and CNE2-CDDP-5Fu against CDDP was 2.63-fold and 5.35-fold stronger than that of parental CNE2, respectively.Of the four ABC transporters (ABCB1, ABCC1, ABCC2 and ABCG2) related to MDR, only ABCC2 was found to be elevated both in CDDP-resistant sublines, with ABCC2 located in nucleus of CNE2-CDDP-5Fu but not in CNE2-CDDP and parental CNE2.Further research showed that compared to untreated CNE2, the intracellular levels of CDDP were decreased by 2.03-fold in CNE2-CDDP and 2.78-fold in CNE2-CDDP-5Fu.

View Article: PubMed Central - PubMed

Affiliation: Cancer Research Institute, Southern Medical University, Guangzhou City, Guangdong Province 510515, China.

ABSTRACT
Cisplatin (CDDP) is one of the most active drugs to treat nasopharyngeal carcinoma (NPC) patients. To further understand the mechanisms of CDDP-resistance in NPC, two CDDP-resistant sublines (CNE2-CDDP and CNE2-CDDP-5Fu) derived from parental NPC cell line CNE2 were established. It was found that at the IC50 level, the resistance of CNE2-CDDP and CNE2-CDDP-5Fu against CDDP was 2.63-fold and 5.35-fold stronger than that of parental CNE2, respectively. Of the four ABC transporters (ABCB1, ABCC1, ABCC2 and ABCG2) related to MDR, only ABCC2 was found to be elevated both in CDDP-resistant sublines, with ABCC2 located in nucleus of CNE2-CDDP-5Fu but not in CNE2-CDDP and parental CNE2. Further research showed that compared to untreated CNE2, the intracellular levels of CDDP were decreased by 2.03-fold in CNE2-CDDP and 2.78-fold in CNE2-CDDP-5Fu. After treatment with PSC833, a modulator of MDR associated transporters including ABCC2, the intracellular level of CDDP was increased in CDDP-resistant sublines, and the resistance to CDDP was partially reversed from 2.63-fold to 1.62-fold in CNE2-CDDP and from 5.35-fold to 4.62-fold in CNE2-CDDP-5Fu. These data indicate that ABCC2 may play an important role in NPC resistant to CDDP.

No MeSH data available.


Related in: MedlinePlus