Mechanism of multidrug resistance of human small cell lung cancer cell line H446/VP.
- Author:
Yan-Ling WANG
1
;
Yun-Li YAN
;
Na-Jing ZHOU
;
Shuo HAN
;
Jun-Xia ZHAO
;
Cui-Li CAO
;
Yu-Hong LÜ
Author Information
- Publication Type:Journal Article
- MeSH: ATP Binding Cassette Transporter, Sub-Family B; ATP-Binding Cassette, Sub-Family B, Member 1; genetics; metabolism; Antigens, Neoplasm; genetics; metabolism; Blotting, Western; Cell Line, Tumor; DNA Topoisomerases, Type II; genetics; metabolism; DNA-Binding Proteins; genetics; metabolism; Drug Resistance, Multiple; genetics; physiology; Drug Resistance, Neoplasm; genetics; physiology; Humans; Immunohistochemistry; Proto-Oncogene Proteins c-bcl-2; genetics; metabolism; Reverse Transcriptase Polymerase Chain Reaction; Small Cell Lung Carcinoma; metabolism
- From: Chinese Medical Journal 2010;123(22):3299-3303
- CountryChina
- Language:English
-
Abstract:
BACKGROUNDSmall cell lung cancer (SCLC) is the most aggressive form of lung cancer. This study aimed to investigate the mechanism of human small cell lung cancer cell line resistance to etoposide (VP-16), H446/VP.
METHODSThe cell viability was measured by MTT assay. Immunocytochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting methods were used to detect the multidrug resistance gene (MDR1), bcl-2, bax and the topoisomerase II (Topo II) expressions in H446 and H446/VP cells after treated with or without VP-16.
RESULTSThe 50% inhibition concentration (IC50) of VP-16 on H446 cells was 49 mg/L, and 836 mg/L was for H446/VP cells. The expressions of MDR1 and bcl-2 were up-regulated, while the amounts of bax and Topo II were reduced in H446/VP cells. After treated with 49 mg/L of VP-16, it showed that the drug could significantly inhibit bcl-2 and Topo II expressions, and increase bax expression in H446 cells compared with that of H446/VP cells.
CONCLUSIONSThe H446/VP cell was stably resistant to VP-16. The decreased expression of Topo II was correlated with the H446/VP multidrug resistance. The elevated expressions of MDR1, and the altered apoptotic pathways also played an important role in VP-16 induced multidrug resistance of SCLC.
