ABCG2-overexpressing S1-M1-80 cell xenografts in nude mice keep original biochemistry and cell biological properties / 癌症

S1-M1-80 cells, derived from human colon carcinoma S1 cells, are mitoxantrone-selected ABCG2-overexpressing cells and are widely used in in vitro studies of multidrug resistance(MDR). In this study, S1-M1-80 cell xenografts were established to investigate whether the MDR phenotype and cell biological properties were maintained in vivo. Our results showed that the proliferation, cell cycle, and ABCG2 expression level in S1-M1-80 cells were similar to those in cells isolated from S1-M1-80 cell xenografts (named xS1-M1-80 cells). Consistently, xS1-M1-80 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan, but remained sensitive to the non-ABCG2 substrate cisplatin. Furthermore, the specific ABCG2 inhibitor Ko143 potently sensitized xS1-M1-80 cells to mitoxantrone and topotecan. These results suggest that S1-M1-80 cell xenografts in nude mice retain their original cytological characteristics at 9 weeks. Thus, this model could serve as a good system for further investigation of ABCG2-mediated MDR.

A cell-based screen for anticancer activity of 13 pyrazolone derivatives / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Pyrazolone derivatives were reported to have a potent cytotoxicity against some tumor cells. In the present study, we evaluated the cytotoxic activity of a series of pyrazolone derivatives against four human tumor cell lines including HepG2, OVCAR3, KB, and multidrug resistance (MDR) KBv200 cell lines in vitro and in vivo. Additionally, the structure-activity relationships of these compounds were discussed.</p><p><b>METHODS</b>To analyze the antiproliferative potential of the synthesized compounds against several human tumor cell lines, the 50% inhibitory concentration (IC50) values were determined by MTT assay. Besides, the KBv200 cell xenograft experimental model was established and the sensitivity to the pyrazolone compounds was compared between drug-sensitive parental KB cells and MDR KBv200 cells.</p><p><b>RESULTS</b>Of 13 compounds screened, compound 9 presented remarkable anticancer effects, of which IC50 values were (3.24 ± 0.28), (2.58 ± 0.61), (3.81 ± 0.02), and (3.45 ± 0.03) μg/mL in HepG2, OVCAR3, KB and MDR KBv200 cells, respectively (P > 0.05). Furthermore, compound 9 effectively inhibited tumor growth of KBv200 cell xenografts in vivo, the inhibition ratio was 25.37%, 38.43%, and 47.50% for 1.5 mg/kg, 3 mg/kg, and 6 mg/kg of compound 9 groups, respectively.</p><p><b>CONCLUSION</b>Compound 9 was the most promising antitumor agent in this study.</p>

Induction of apoptosis of tumor multidrug resistance cell by uvarigrin and its mechanism / 药学学报

<p><b>AIM</b>To study the effect of uvarigrin on mitochondrial dependent pathway during the apoptosis induced by it in MDR KBv200 cells and their parental sensitive KB cells.</p><p><b>METHODS</b>MTT assay was used to detect the cytotoxic effect of uvarigrin on KBv200 and KB cells. Annexin V FITC staining identified uvarigrin-induced apoptosis in KBv200 and KB cells. These cells underwent incubation with DCFH-DA, or DiOC6, followed by flowcytometry for the measurement of reactive oxygen species (ROS) and mitochondrial membrane potential (deltapsim), respectively. The Western blotting analysis was performed on Caspase-9 activation.</p><p><b>RESULTS</b>Uvarigrin inhibited the growth of KBv200 cells and KB cells in vitro. Most of the uvarigrin-induced cells death was found to be due to apoptosis, as determined by Annexin V FITC staining. During the apoptosis, the level of ROS increased while the level of deltapsim decreased in a time-dependent manner. Uvarigrin triggered Caspase-9 activation.</p><p><b>CONCLUSION</b>Uvarigrin induced apoptosis in KBv200 cells and KB cells probably through a mitochondria-dependent pathway.</p>

Effects of Chansu injection on transplanting-tumor models S180 in mice and human colon cancer HT-29 in nude mice / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To study the antitumor effects of Chansu injection on transplanting- tumor of S(180 ) in mice and human colon cancer HT-29 in nude mice.</p><p><b>METHODS</b>Using transplanting- tumor models of S(180 ) in mice and human colon cancer HT-29 in nude mice,the tumor inhibitive ratio(IR) of Chansu injection was determined and apoptosis was microscopically observed.</p><p><b>RESULTS</b>Compared with tumor-negative control groups, IR at different dosage of Chansu in models of S(180) and HT-29 was 19.1% - 38.2% and 9.5% - 15.8% respectively,there was a dose-dependent relationship in models of S ( 180) (P< 0.05) and HT- 29 (P> 0.05). The tumor growth was markedly inhibited by cyclophosphamide (CTX) in model of S( 180) with IR of 70.7% and in model of HT-29 with IR of 67.1%, compared with control groups, both P< 0.01; apoptosis induced by CTX was markedly observed by in microscope examination. No significant side effects were shown in the study group.</p><p><b>CONCLUSIONS</b>Chansu injection can significantly inhibit tumor growth in model of S(180), but not in model of HT- 29. Different type of tumor has different drug-sensitivity.</p>

Experimental chemotherapy against xenografts derived from multidrug resistant KBv200 cells and parental drug-sensitive KB cells in nude mice by annonaceous acetogenin 89-2 / 药学学报

<p><b>AIM</b>Annonaceous acetogenin 89-2 was obtained from atemoya plant. To investigate the effect of 89-2 on experimental chemotherapy against xenografts derived from multidrug resistant KBv200 cells and parental drug-sensitive KB cells.</p><p><b>METHODS</b>Cytotoxicity was determined by tetrazolium (MTT) assay. The models of KB and KBv200 xenografts in nude mice were established to investigate the effect of 89-2 on experimental chemotherapy against cancer in vivo. Mechanistic experiments were conducted to examine the function of P-gp by Fura 2-AM assay.</p><p><b>RESULTS</b>The compound 89-2 showed potent cytotoxicity in KBv200 and KB cells, and the mean IC50 of 89-2 to KBv200 and KB cells was 48.7 and 64.6 nmol.L-1, respectively. The IC50 of 89-2 to multidrug resistant (MDR) cells was similar to that to the parental drug-sensitive cells (P < 0.05). In the models of KBv200 and KB cell xenografts in nude mice, 89-2 (0.90 mg.kg-1, q2d x 6) exhibited 52.3% and 56.5% in inhibiting the growth of xenografts, respectively. The toxicity was endurable. The intracellular accumulation of Fura-2 in KBv200 cells increased to 1.66, 2.03, and 2.74-fold, respectively, by addition of 12.8, 64 and 320 nmol.L-1 of 89-2.</p><p><b>CONCLUSION</b>Both MDR KBv200 cells and parental drug-sensitive KB cells were sensitive to the treatment of 89-2 in vitro and in vivo. The mechanism of overcoming MDR was associated with the decrease of P-gp function MDR cells.</p>