W J Hou1, J H Guan, Q Dong, Y H Han, R Zhang. 1. Department of Obstetrics and Gynecology, Shanghai Jiaotong University-Affiliated Sixth People's Hospital of Fengxian Branch, Shanghai, China. ronggzhang@hotmail.com.
Abstract
BACKGROUND: Recent studies showed that dexamethasone (DEX) could render cancer cells resistant to paclitaxel (PTX) induced apoptosis though an unknown mechanism. AIM: This study aimed to evaluate the influence of DEX pretreatment on the anti-tumor effect of PTX in an in vivo xenograft model with grafted ovarian cancer SKOV-3 cells innude mice. MATERIALS AND METHODS: The xenograft procedure was performed, and the nude mice were grouped into four cohorts of ten that received the following treatments: Control group, DEX group, PTX group and DEX+PTX group. Individual treatments were administered once every three days for a total of 6 courses. The growth of tumors and the inhibition rates were measured. Changes in tissue morphology and cellular ultrastructure were observed using light and transmission electron microscopy. Immunohistochemistry was performed to examine the expression of Ki-67, Bcl-xL and cleaved caspase-3. RESULTS: Premedication with DEX reduced the inhibitory effect of PTX on tumor growth by approximately 20% compared to the PTX-only-treated group in the ovarian carcinoma xeno-grafted mice. Hematoxylin-eosin (H&E) staining revealed that significantly fewer cells exhibited vacuolization and apoptosis in the DEX + PTX group compared to the PTX group. Apoptotic characteristics including karyopyknosis, nuclear chromatin condensation along the nuclear membrane and aggregation were observed in both DEX+PTX and PTX groups under electron microscopy. However, these characteristics were less significant in the DEX+PTX group than those in the PTX group. The immunohistochemistry demonstrated that protein expression levels of Ki-67 and Bcl-xL were significantly increased, whereas cleaved caspase-3 decreased in the DEX+PTX group, compared to PTX group (p < 0.0125). CONCLUSIONS: DEX inhibits the therapeutic efficacy of PTX in a human ovarian carcinoma SKOV-3 xenograft model.
BACKGROUND: Recent studies showed that dexamethasone (DEX) could render cancer cells resistant to paclitaxel (PTX) induced apoptosis though an unknown mechanism. AIM: This study aimed to evaluate the influence of DEX pretreatment on the anti-tumor effect of PTX in an in vivo xenograft model with grafted ovarian cancer SKOV-3 cells innude mice. MATERIALS AND METHODS: The xenograft procedure was performed, and the nude mice were grouped into four cohorts of ten that received the following treatments: Control group, DEX group, PTX group and DEX+PTX group. Individual treatments were administered once every three days for a total of 6 courses. The growth of tumors and the inhibition rates were measured. Changes in tissue morphology and cellular ultrastructure were observed using light and transmission electron microscopy. Immunohistochemistry was performed to examine the expression of Ki-67, Bcl-xL and cleaved caspase-3. RESULTS: Premedication with DEX reduced the inhibitory effect of PTX on tumor growth by approximately 20% compared to the PTX-only-treated group in the ovarian carcinoma xeno-grafted mice. Hematoxylin-eosin (H&E) staining revealed that significantly fewer cells exhibited vacuolization and apoptosis in the DEX + PTX group compared to the PTX group. Apoptotic characteristics including karyopyknosis, nuclear chromatin condensation along the nuclear membrane and aggregation were observed in both DEX+PTX and PTX groups under electron microscopy. However, these characteristics were less significant in the DEX+PTX group than those in the PTX group. The immunohistochemistry demonstrated that protein expression levels of Ki-67 and Bcl-xL were significantly increased, whereas cleaved caspase-3 decreased in the DEX+PTX group, compared to PTX group (p < 0.0125). CONCLUSIONS:DEX inhibits the therapeutic efficacy of PTX in a humanovarian carcinoma SKOV-3 xenograft model.
Authors: Shonagh Russell; Felicia Lim; Pamela N Peters; Suzanne E Wardell; Regina Whitaker; Ching-Yi Chang; Rebecca A Previs; Donald P McDonnell Journal: Cancers (Basel) Date: 2022-08-30 Impact factor: 6.575