The mechanism of topotecan resistance in ovarian cancer cell line / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To study the mechanism of topotecan (TPT) resistance in ovarian cancer cell line.</p><p><b>METHODS</b>A TPT-resistant ovarian cancer cell line A2780/TPT established in this laboratory was used in this study. Intracellular rhodamine fluorescence intensity of the TPT-resistant cells and parental cells were measured by flow cytometry. The gene expression of membrane protein transporter such as transporter P-glycoprotein (P-gp), multidrug resistance associated protein (MRP), breast cancer resistance protein (BCRP) was evaluated by RT-PCR. The antisense-phosphorothioate oligonucleotide (ASODN) including a translation initiation site of BCRP mRNA was transferred into resistant cells by liposome.</p><p><b>RESULTS</b>Intracellular rhodamine fluorescence intensity of the resistant cells was 31.19% of that in the parental cells (P < 0.01). No expression of P-gp was demonstrated, and that of MRP was very weak in the TPT-resistant cells (relative expression value = 0.057). BCRP was overexpressed in the TPT-resistant cells (relative expression = 0.66), but not in the parental cells. Transfer of ASODN into resistant cells resulted in a 59.42% reduction of BCRP gene expression (P < 0.05) and an obviously increased intracellular rhodamine fluorescence intensity from 5.42 to 16.63 (P < 0.05).</p><p><b>CONCLUSION</b>The overexpression of BCRP which mediated drug efflux may play an important role in the induction of TPT-resistance in ovarian cancer.</p>

Correlation of expression of RhoA (RhoC and their effector ROCK-1 with malignant phenotype of ovarian cancer cells in vitro / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of RhoA, RhoC and their effector ROCK-1 in four ovarian cancer cell lines in vitro and their correlation with invasiveness.</p><p><b>METHODS</b>Expression of RhoA, RhoC and ROCK-1 mRNA and protein in four ovarian cancer cell lines SW626, Skov-3, A2780 and Caov-3 was detected by RT-PCR and Western blot assay. Invasion assay was done in Boyden chamber.</p><p><b>RESULTS</b>The expression levels of RhoA, RhoC and ROCK-1 mRNA and protein varied in the four different cell lines examined. The expression level of RhoC, but not RhoA and ROCK-1, was significantly correlated with the invasive capability of these cells in vitro (r = 0.95, P < 0.01). Expression of RhoA at the level of transcription was not correlated with that at the translation level. The expression of RhoA and RhoC did not correlate with that of ROCK-1.</p><p><b>CONCLUSION</b>Expression level of RhoC may serve as an independent parameter in evaluating metastasis and become a new target in inhibiting ovarian cancer metastasis.</p>

Significance of expression of T lymphoma invasion/metastasis gene in ovarian cancer cells / 中国医学科学院学报

<p><b>OBJECTIVE</b>To study the role of T lymphoma invasion/metastasis gene 1 (Tiam1) and protein in ovarian tumor cells.</p><p><b>METHODS</b>Expressions of Tiam1 mRNA, Rac1 mRNA, and Tiam1 protein in four ovarian tumor cells A2780, Caov3, Skov3, and SW626 were studied by using RT-PCR and Western blot, respectively. The cell migration ability was analyzed by in vitro invasion assay.</p><p><b>RESULTS</b>Expressions of Tiam1 mRNA and protein, as well as Rac1 mRNA were detected in all four ovarian tumor cells. There was a strong direct correlation between the levels of Tiam1 and Rac1 mRNA expression and migration potentials of all four ovarian cancer cells in vitro experiments. The increased expressions of Tiam1 mRNA were coincident with those of Rac1 mRNA, with a parallel relationship (P = 0.003, r = 0.874). Levels of Rac1 mRNA expression were significantly correlated with the potentials of tumor cell migration (P = 0.042, r = 0.814).</p><p><b>CONCLUSION</b>Tiam1-Rac1 signaling pathway plays a positive role in assessing tumor cell invasion and metastasis and provides a new target for gene therapy of ovarian cancer.</p>