Combination of γ-radiation antagonizes the cytotoxic effects of vincristine and vinblastine on both mitotic arrest and apoptosis

Sui, Meihua; Fan, Weimin

doi:10.1016/j.ijrobp.2004.12.028

Cited by 21 publications

(26 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The cytotoxicity of vinca alkaloids, 17-b-estradiol, and their combination was further evaluated with clonogenic assays according to the method described previously [29,30]. Briefly, cells were plated on six-well plates (35 mm) with 200-25,000 cells/well based upon the concentration of drugs to achieve 50-200 colonies/well.…”

Section: Clonogenic Assaymentioning

confidence: 99%

Fulvestrant (ICI 182,780) sensitizes breast cancer cells expressing estrogen receptor α to vinblastine and vinorelbine

Sui

Jiang

Hinsch

et al. 2009

Breast Cancer Res Treat

Self Cite

View full text Add to dashboard Cite

Cumulative data suggest that some chemotherapeutic agents may be less effective in estrogen receptor alpha positive (ER+) breast tumors than ER negative (ER-) tumors, which has raised a clinically relevant question as to how to reverse this ER-mediated chemoresistance in ER+ breast tumors. This study is to investigate the possible influence of estrogen receptor alpha (ERalpha) on the therapeutic effects of vinblastine and vinorelbine on breast cancer cells and explore whether combination of anti-estrogen agent fulvestrant (ICI 182, 780) may enhance the sensitivity of ERalpha+ cells to these chemotherapeutic agents. Through comparing ER+ with ER- human breast tumor cells or through stable transfection of an ERalpha expression vector into ER negative human breast cancer BCap37 cells, a series of assays were applied to determine the sensitivity of ER+ and ER- breast tumor cells to vinblastine and vinorelbine in the presence or absence of 17-beta-estradiol and/or fulvestrant. 17-beta-Estradiol showed no effect on the sensitivity of ER- MDA-MB-468 and BCap37 cells to the treatment of vincristine or vinblastine, but it significantly reduced the sensitivity of ER+ T47D cells and BCap37 cells expressing ERalpha to the two drugs mentioned. Further analyses show that ERalpha has little effect on vinca alkaloids-induced mitotic arrest, but dramatically affects their ability to induce tumor cell apoptosis. Moreover, through a series of assays, we also demonstrated that the combination of fulvestrant, a selective ER down-regulator, could reverse the resistance of ER+ breast tumor cells to vinca alkaloids and even produce synergistic effects. The findings obtained from this study have provided important evidence that expression and subsequent activation of ERalpha are associated with resistance of breast cancer cells to vinca alkaloids. This study also suggested that the combination of anti-estrogen agents, such as fulvestrant, might be a novel strategy to reverse ER-mediated chemoresistance or sensitize ER+ breast tumors to vinca alkaloids and possibly other chemotherapeutic agents.

show abstract

Section: Clonogenic Assaymentioning

confidence: 99%

Fulvestrant (ICI 182,780) sensitizes breast cancer cells expressing estrogen receptor α to vinblastine and vinorelbine

Sui

Jiang

Hinsch

et al. 2009

Breast Cancer Res Treat

Self Cite

View full text Add to dashboard Cite

show abstract

“…13,14 Briefly, 4 lm paraffin-embedded tissue sections were prepared from the human xenograft tumors after single treatment for 48 hr. The slides were then subjected to TUNEL staining using an In Situ Cell Death Dectection Kit according to the manufacturer's protocol (Roche, Penzberg, Germany).…”

Section: Tdt-mediated Dutp Nick End Labeling Assaymentioning

confidence: 99%

Glucocorticoids interfere with therapeutic efficacy of paclitaxel against human breast and ovarian xenograft tumors

Sui¹,

Chen²,

Chen³

et al. 2006

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

Paclitaxel is a widely used naturally occurring antineoplastic agent that has shown great promise in the treatment of a variety of human solid tumors, particularly for advanced breast and ovarian cancers. Recent studies in our laboratory discovered that glucocorticoids could selectively inhibit paclitaxel-induced apoptosis in a number of human solid tumor cell lines in vitro. Since glucocorticoids (such as dexamethasone) are routinely used as a premedication in the clinical application of paclitaxel to prevent hypersensitivity reactions and other adverse effects, the inhibitory effect of glucocorticoids on paclitaxel-induced apoptosis has raised a clinically relevant question as to whether the pretreatment with glucocorticoids might interfere with the therapeutic efficacy of paclitaxel. In the present study, through development of animal models bearing human breast and ovarian xenograft tumors, we evaluated the potential influence of dexamethasone on antitumor activity of paclitaxel in vivo. The results demonstrated that pretreatment of dexamethasone significantly attenuated therapeutic efficacy of paclitaxel against human breast and ovarian xenograft tumors. The inhibition rate of 20 mg paclitaxel/kg on the growth of breast and ovarian xenograft tumors was around 20-25% less when the animals were pretreated with 1 mg dexamethasone/kg. Further analyses with histological examination and TdT-mediated dUTP nick end labeling assay indicate that pretreatment with dexamethasone clearly interferes with the cytotoxic effects of paclitaxel on both morphological alterations and induction of cell death. Additionally, immunohistochemical staining of proliferation marker Ki-67 indicates that the percentage of proliferating cells in xenograft tumors with pretreatment of dexamethasone is much higher than that in the tumors treated with paclitaxel alone. Put together, the results obtained from the animal experiments show that pretreatment of xenograft tumors with dexamethasone results in significant inhibition of the therapeutic efficacy of paclitaxel in vivo. This finding may have a potential implication on the clinical practice of paclitaxel-based chemotherapy. ' 2006 Wiley-Liss, Inc.Key words: paclitaxel; dexamethasone; xenografts; apoptosis; breast cancer Paclitaxel (Taxol 1 ), a naturally occurring antineoplastic agent, has shown great promise in the therapeutic treatment of certain human solid tumors, particularly for metastatic breast cancer and drug-refractory ovarian cancer.1,2 In recent years, it has been well recognized that paclitaxel, in addition to its classical activities in inducing microtubule bundling and mitotic arrest, possesses significant cell-killing activity against tumor cells through induction of apoptosis, although the mechanism by which paclitaxel induces apoptotic cell death is not entirely clear. Recent studies in our laboratory discovered that glucocorticoids selectively inhibited paclitaxel-induced apoptosis in a number of human solid tumor cell lines, but did not affect the ability of paclitaxel...

show abstract

“…The TUNEL assay was carried out using the method previously described (26)(27)(28). Briefly, cells were trypsinized and affixed to slides by using a Cytospin 3 (Shandon) cell preparation system after various treatments.…”

Section: Introductionmentioning

confidence: 99%

Estrogen Receptor α Mediates Breast Cancer Cell Resistance to Paclitaxel through Inhibition of Apoptotic Cell Death

et al. 2007

Self Cite

View full text Add to dashboard Cite

Estrogen receptors (ER) are expressed in f65% of human breast cancer. Cumulative data from clinical trials and retrospective analyses suggest that some chemotherapeutic agents may be less effective in patients with ER-positive (ER+) tumors than those with ER-negative (ERÀ) tumors. Paclitaxel is an active agent used in breast cancer chemotherapy. To investigate the possible influence of ER on the therapeutic efficacy of paclitaxel and its underlying mechanism, we established several isogenic ER+ cell lines by stable transfection of ERA expression vectors into ERÀ breast cancer BCap37 cells. We showed that 17-B estradiol significantly reduces the overall cytotoxicity of paclitaxel in BCap37-expressing ERA but has no influence on the ERÀ parental cells. Further analyses indicate that expression of ERA in BCap37 cells mainly interferes with paclitaxel-induced apoptotic cell death, without affecting paclitaxel-induced microtubule bundling and mitotic arrest. Moreover, we found that the addition of ICI 182,780 (Fulvestrant), a selective ER down-regulator, could completely reverse the resistance of ER+ BCap37 cells to paclitaxel. These findings showed that ERA-mediated breast tumor cell resistance to paclitaxel was through selective inhibition of paclitaxel-induced tumor cell apoptosis. Additionally, the combination of ICI 182,780 also sensitizes MCF-7 and T47D cell lines to the treatment of paclitaxel, which further confirmed the correlation between ERA and drug resistance in ER+ tumor cells. The results obtained from this study provide useful information for understanding ERmediated resistance to paclitaxel and possibly other antineoplastic agents. [Cancer Res 2007;67(11):5337-44]

show abstract

Combination of γ-radiation antagonizes the cytotoxic effects of vincristine and vinblastine on both mitotic arrest and apoptosis

Cited by 21 publications

References 27 publications

Fulvestrant (ICI 182,780) sensitizes breast cancer cells expressing estrogen receptor α to vinblastine and vinorelbine

Fulvestrant (ICI 182,780) sensitizes breast cancer cells expressing estrogen receptor α to vinblastine and vinorelbine

Glucocorticoids interfere with therapeutic efficacy of paclitaxel against human breast and ovarian xenograft tumors

Estrogen Receptor α Mediates Breast Cancer Cell Resistance to Paclitaxel through Inhibition of Apoptotic Cell Death

Contact Info

Product

Resources

About