Effect Of Celecoxib On Migration And Invasion Of Breast Cancer Cell And The Sensitization Effect Of Chemotherapy

Background and Objective: Breast cancer is one of the most commonmalignancies of women, which is serious harm to women’s health. Surgery was themainstay of treatment modality in early breast cancer, but in advanced breast cancermetastasis has often occurred with less chance of surgery, treatment methods includeradiotherapy, chemotherapy and traditional Chinese herb will be considered.Therefore, to effectively inhibit the metastasis of breast cancer research isincreasingly becoming the focus. Studies show that cyclooxygenase-2(COX-2) playsa very important role in breast cancer and other malignancies. A new generation ofnon-steroidal anti-inflammatory drugs celecoxib can specifically inhibit COX-2synthesis, thereby inhibiting tumor cell growth, and increase the efficacy ofconventional chemotherapy drugs. However, it has not yet been reported that effect ofcelecoxib in breast cancer invasion and metastasis and the role of combination therapy.This study aimed to further investigate the effects of the new non-steroidalanti-inflammatory drugs on invasion of MCF-7human breast cancer cell line and itsmechanism through a series of in vitro experiments and explore the sensitizing effectof celecoxib on doxorubicin in combined treatment of breast cancer.Methods:(1) MTS assay was performed to measure the effect of celecoxib aloneand with doxorubicin on breast cancer cell growth and proliferation;(2) Plate cloningmethod and soft agar colony formation assay were used to detect inhibitory effect ofcelecoxib on MCF-7cell growth and proliferation capacity;(3)&(4) Scratching assayand transwell method were used to measure the effect of celecoxib on the migrationand invasion/metastasis abilities of MCF-7cells in vitro respectively;(5) The changesof COX-2, VEGF-a and MMP9expression after celecoxib treatment in MCF-7cellswere surveyed by Western blotting.Results：(1) Celecoxib can inhibit proliferative activity of MCF-7cell in atime-dependent manner and a dose-dependent manner，and its IC50is33.62μg/mL at48hafter treatment;(2) Celecoxib inhibits anchorage-dependent growth of MCF-7cellin a dose-dependent manner, colony forming efficiency in50.0μg/mL celecoxibtreatment group and25.0μg/mL celecoxib treatment group decreased by7.78timesand3.2times respectively compared to the control group, and the differences weresignificant (P<0.01);(3) Celecoxib inhibits anchorage-independent growth of MCF-7 cell in a dose-dependent manner, colony formation inhibition rates of12.5μg/mL,25.0μg/mL and50.0μg/mL celecoxib treatment group on MCF-7cells in soft agarwere27.37%,58.64%and88.76%respectively;(4) Celecoxib significantly inhibitedmigration of MCF-7cells, and cell confluency of treatment group decreased12.6times compared to control group;(5) Celecoxib reduces invasion ability of MCF-7cell, and cells trans-membrane of celecoxib treatment group(50.0μg/mL) wassignificantly lower than that in control group (respectively,5.3±0.42and89.2±7.78), the difference was significant (P<0.01);(6)25.0μg/mL celecoxib can lead toIC50values of ADM reduction in MCF-7cells from6.651μg/mL to1.783μg/mL;(7)Celecoxib can down-regulate the expressions of COX-2、VEGF-a and MMP-9in adose-dependent manner.Conclusion:(1) celecoxib can inhibit the proliferation and abilities of migrationand migration/invasion in vitro of human breast cancer MCF-7cell;(2) The effects ofgrowth and invasion inhibition of celecoxib on MCF-7cells may be related toinhibition of COX-2and then inhibition of expression of VEGF-a and MMP-9;(3)celecoxib can increase the sensitivity of MCF-7to ADM, which may be related to theabove-mentioned mechanism.