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Gemcitabine eliminates double minute chromosomes from human ovarian cancer cells.

Yu L, Zhao Y, Quan C, Ji W, Zhu J, Huang Y, Guan R, Sun D, Jin Y, Meng X, Zhang C, Yu Y, Bai J, Sun W, Fu S - PLoS ONE (2013)

Bottom Line: Amplified genes present on the double minute chromosomes are decreased at the DNA level upon gemcitabine treatment.Cells treated with gemcitabine also showed decreased cell growth, colony formation, and invasion.Together, our results suggest that gemcitabine is effective in decreasing double minute chromosomes and this affects the biology of ovarian cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.

ABSTRACT
Double minute chromosomes are cytogenetic manifestations of gene amplification frequently seen in cancer cells. Genes amplified on double minute chromosomes include oncogenes and multi-drug resistant genes. These genes encode proteins which contribute to cancer formation, cancer progression, and development of resistance to drugs used in cancer treatment. Elimination of double minute chromosomes, and therefore genes amplified on them, is an effective way to decrease the malignancy of cancer cells. We investigated the effectiveness of a cancer drug, gemcitabine, on the loss of double minute chromosomes from the ovarian cancer cell line UACC-1598. Gemcitabine is able to decrease the number of double minute chromosomes in cells at a 7500X lower concentration than the commonly used cancer drug hydroxyurea. Amplified genes present on the double minute chromosomes are decreased at the DNA level upon gemcitabine treatment. Gemcitabine, even at a low nanomolar concentration, is able to cause DNA damage. The selective incorporation of double minutes chromatin and γ-H2AX signals into micronuclei provides a strong link between DNA damage and the loss of double minute chromosomes from gemcitabine treated cells. Cells treated with gemcitabine also showed decreased cell growth, colony formation, and invasion. Together, our results suggest that gemcitabine is effective in decreasing double minute chromosomes and this affects the biology of ovarian cancer cells.

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Treatment with HU or GEM decreases the malignancy of UACC-1598 ovarian cancer cells.A. The growth of UACC-1598 cells is decreased when grown in the presence of HU or GEM. The OD value of cells were measured every day for 6 days and plotted as mean ± SD. **denotes a P value of 0.001 to 0.01 from day 4 onwards when compared to the control group. B. Colony formation of UACC-1598 cells is decreased when grown in the presence of HU or GEM. The average numbers of colonies ± SD decreased from 365±24 colonies to 182±30 for HU treated cells and 168±25 for GEM treated cells. ***denotes a P value of <0.001 when compared to the control group. C. One representative trial of cell invasion is plotted for Ctrl., HU treated, and GEM treated cells. The invasion percentage of cells decreased from 0.58% for control group to 0.20% for HU treated cells and 0.35% for GEM treated cells. ***denotes a P value of <0.001 when compared to the control group.
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pone-0071988-g007: Treatment with HU or GEM decreases the malignancy of UACC-1598 ovarian cancer cells.A. The growth of UACC-1598 cells is decreased when grown in the presence of HU or GEM. The OD value of cells were measured every day for 6 days and plotted as mean ± SD. **denotes a P value of 0.001 to 0.01 from day 4 onwards when compared to the control group. B. Colony formation of UACC-1598 cells is decreased when grown in the presence of HU or GEM. The average numbers of colonies ± SD decreased from 365±24 colonies to 182±30 for HU treated cells and 168±25 for GEM treated cells. ***denotes a P value of <0.001 when compared to the control group. C. One representative trial of cell invasion is plotted for Ctrl., HU treated, and GEM treated cells. The invasion percentage of cells decreased from 0.58% for control group to 0.20% for HU treated cells and 0.35% for GEM treated cells. ***denotes a P value of <0.001 when compared to the control group.

Mentions: We also tested whether addition of low levels of GEM affects the biological properties of ovarian cancer cells. By using the MTS assay, we observed a significant decrease from day four onward for UACC-1598 cells grown in the presence of either 150 µM HU or 20 nM GEM (Figure 7A). In addition, we also observed a significant decrease in colony formation for cells treated with either of the two compounds. The average number of colonies from the same plating number decreased from 365±24 colonies to 182±30 for HU treated cells and 168±25 for GEM treated cells (Figure 7B). Furthermore, we also observed a decrease in invasion for HU and GEM treated cells. The percentage of cells invading through the membrane for one experiment is plotted, which decreased from 0.58% for control group to 0.20% for HU treated cells and 0.35% for GEM treated cells (Figure 7C). Two other repeats show similar results. The percentage of cells invading through the membrane decreased from an average of 42% for control cells to 23% and 24% for HU and GEM treated cells respectively (data not shown). Taken together, these data shows that in addition to affecting double minute chromosomes, GEM also affects the biological properties of ovarian cancer cells.


Gemcitabine eliminates double minute chromosomes from human ovarian cancer cells.

Yu L, Zhao Y, Quan C, Ji W, Zhu J, Huang Y, Guan R, Sun D, Jin Y, Meng X, Zhang C, Yu Y, Bai J, Sun W, Fu S - PLoS ONE (2013)

Treatment with HU or GEM decreases the malignancy of UACC-1598 ovarian cancer cells.A. The growth of UACC-1598 cells is decreased when grown in the presence of HU or GEM. The OD value of cells were measured every day for 6 days and plotted as mean ± SD. **denotes a P value of 0.001 to 0.01 from day 4 onwards when compared to the control group. B. Colony formation of UACC-1598 cells is decreased when grown in the presence of HU or GEM. The average numbers of colonies ± SD decreased from 365±24 colonies to 182±30 for HU treated cells and 168±25 for GEM treated cells. ***denotes a P value of <0.001 when compared to the control group. C. One representative trial of cell invasion is plotted for Ctrl., HU treated, and GEM treated cells. The invasion percentage of cells decreased from 0.58% for control group to 0.20% for HU treated cells and 0.35% for GEM treated cells. ***denotes a P value of <0.001 when compared to the control group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3750019&req=5

pone-0071988-g007: Treatment with HU or GEM decreases the malignancy of UACC-1598 ovarian cancer cells.A. The growth of UACC-1598 cells is decreased when grown in the presence of HU or GEM. The OD value of cells were measured every day for 6 days and plotted as mean ± SD. **denotes a P value of 0.001 to 0.01 from day 4 onwards when compared to the control group. B. Colony formation of UACC-1598 cells is decreased when grown in the presence of HU or GEM. The average numbers of colonies ± SD decreased from 365±24 colonies to 182±30 for HU treated cells and 168±25 for GEM treated cells. ***denotes a P value of <0.001 when compared to the control group. C. One representative trial of cell invasion is plotted for Ctrl., HU treated, and GEM treated cells. The invasion percentage of cells decreased from 0.58% for control group to 0.20% for HU treated cells and 0.35% for GEM treated cells. ***denotes a P value of <0.001 when compared to the control group.
Mentions: We also tested whether addition of low levels of GEM affects the biological properties of ovarian cancer cells. By using the MTS assay, we observed a significant decrease from day four onward for UACC-1598 cells grown in the presence of either 150 µM HU or 20 nM GEM (Figure 7A). In addition, we also observed a significant decrease in colony formation for cells treated with either of the two compounds. The average number of colonies from the same plating number decreased from 365±24 colonies to 182±30 for HU treated cells and 168±25 for GEM treated cells (Figure 7B). Furthermore, we also observed a decrease in invasion for HU and GEM treated cells. The percentage of cells invading through the membrane for one experiment is plotted, which decreased from 0.58% for control group to 0.20% for HU treated cells and 0.35% for GEM treated cells (Figure 7C). Two other repeats show similar results. The percentage of cells invading through the membrane decreased from an average of 42% for control cells to 23% and 24% for HU and GEM treated cells respectively (data not shown). Taken together, these data shows that in addition to affecting double minute chromosomes, GEM also affects the biological properties of ovarian cancer cells.

Bottom Line: Amplified genes present on the double minute chromosomes are decreased at the DNA level upon gemcitabine treatment.Cells treated with gemcitabine also showed decreased cell growth, colony formation, and invasion.Together, our results suggest that gemcitabine is effective in decreasing double minute chromosomes and this affects the biology of ovarian cancer cells.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Medical Genetics, Harbin Medical University, Harbin, China.

ABSTRACT
Double minute chromosomes are cytogenetic manifestations of gene amplification frequently seen in cancer cells. Genes amplified on double minute chromosomes include oncogenes and multi-drug resistant genes. These genes encode proteins which contribute to cancer formation, cancer progression, and development of resistance to drugs used in cancer treatment. Elimination of double minute chromosomes, and therefore genes amplified on them, is an effective way to decrease the malignancy of cancer cells. We investigated the effectiveness of a cancer drug, gemcitabine, on the loss of double minute chromosomes from the ovarian cancer cell line UACC-1598. Gemcitabine is able to decrease the number of double minute chromosomes in cells at a 7500X lower concentration than the commonly used cancer drug hydroxyurea. Amplified genes present on the double minute chromosomes are decreased at the DNA level upon gemcitabine treatment. Gemcitabine, even at a low nanomolar concentration, is able to cause DNA damage. The selective incorporation of double minutes chromatin and γ-H2AX signals into micronuclei provides a strong link between DNA damage and the loss of double minute chromosomes from gemcitabine treated cells. Cells treated with gemcitabine also showed decreased cell growth, colony formation, and invasion. Together, our results suggest that gemcitabine is effective in decreasing double minute chromosomes and this affects the biology of ovarian cancer cells.

Show MeSH
Related in: MedlinePlus