ABSTRACT
<p><b>BACKGROUND</b>Small 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.</p><p><b>METHODS</b>The 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.</p><p><b>RESULTS</b>The 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.</p><p><b>CONCLUSIONS</b>The 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.</p>
Subject(s)
Humans , ATP Binding Cassette Transporter, Subfamily B , ATP Binding Cassette Transporter, Subfamily 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 , Immunohistochemistry , Proto-Oncogene Proteins c-bcl-2 , Genetics , Metabolism , Reverse Transcriptase Polymerase Chain Reaction , Small Cell Lung Carcinoma , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of IL-24 expression on the growth of glioma cells.</p><p><b>METHODS</b>The IL-24 gene was transfected into rat glioma C6 cells with a retroviral vector. The expression of IL-24 in C6/IL-24 glioma cells was confirmed by RT-PCR. MTT assay and flow cytometry were used to study tumor cell proliferation in vitro. Tumorigenicity in vivo was studied in inbred SD male rats by the growth of intracerebrally inoculated tumor.</p><p><b>RESULTS</b>It was confirmed by RT-PCR that the exogenous IL-24 gene expressed in C6/IL-24 cell. The C6/IL-24 cell proliferation in vitro and tumorigenicity in vivo were both inhibited compared with its parental C6 cell.</p><p><b>CONCLUSION</b>IL-24 expression in glioma cells somehow inhibits their growth in vitro and in vivo.</p>
Subject(s)
Animals , Male , Rats , Brain Neoplasms , Metabolism , Pathology , Cell Line, Tumor , Cell Proliferation , Genetic Vectors , Glioma , Metabolism , Pathology , Interleukins , Genetics , Neoplasm Transplantation , Rats, Sprague-Dawley , Recombinant Proteins , Genetics , Retroviridae , GeneticsABSTRACT
Cyclin B1, a positive regulator, controls mitosis occurrence, plays an important role in cell proliferation. To investigate the clinical significance of cyclin B1, the expression of cyclin B1 in acute leukemia (AL) patients was measured; the expression of cyclin B1 and p21(cipl), and their cell cycle distribution were assayed by flow cytometry in 136 adult patients with newly diagnosed AL, 10 continuous complete remission (CCR) AL and 17 normal controls; the mRNA of cyclin B1 and p21(cipl), and the proliferation cell nuclear antigen (PCNA) in patients and normal controls were detected with semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). The results showed that the expression of cyclin B1 in newly diagnosed AL patients was significantly higher than that in normal controls. For the relapsed AL patients, the cyclin B1 expression was also higher than that in normal controls, but lower than that in newly diagnosed cases, there was no significant difference between the remission cases and normal controls, nor difference between CCR AL patients and normal controls. All patients with high cyclin B1 expression had an unscheduled expression manner, that cyclin B1 protein appeared in G(1) phase, and in some case it even higher than that of G(2) phase. The response rate (partial remission + complete remission) and survival rate in the cyclin B1 high expressed patients were higher than that of cyclin B1 low expressed patients. The relapse rate in cyclin B1 high expressed patients was higher than that in cyclin B1 normally expressed patients. The survival rate in cyclin B1 high expressed patients was higher than that in cyclin B1 low expression patients. A negative correlation between the expression of cyclin B1 and p21(cipl) was observed. Additionally, cyclin B1 protein expression was generally correlated with proliferation index (PI) and proliferation cell nuclear antigen (PCNA). It is concluded that this study demonstrates for the first time cyclin B1 overexpression and abnormally distribution in cell cyclin of newly diagnosed AL patients. It was considered that cyclin B1 may play an important role in leukemic pathogeneses and can be one of the factors influencing the prognosis of AL patients.