Abstract | OBJECTIVE: To investigate the changes of drug sensitivity of spindle poison-induced polyploid tumor cells to chemotherapeutic agents and its possible mechanism. METHODS:
Nocodazole in a dose of 100 ng/ml was used to induce polyploidization in a breast cancer cell line MDA-MB-231 cells. The polyploid cells (T-MDA-MB-231) were sorted by flow cytometry. The morphological changes and proliferation of T-MDA-MB-231 cells were compared with that of MDA-MB-231 cells. The cell growth inhibition was assessed by MTT assay. The cells were treated with paclitaxel, docetaxel, vincristine, epirubicin, 5-Fu, VP16 and oxaliplatin, respectively. Those cells were labeled with annexin V-FITC/PI and analyzed by flow cytometry. Bcl-2 was knocked down in T-MDA-MB-231 cells using SiRNA and their growth inhibition was evaluated by MTT assay to evaluate the reversing effect of Bcl-2-silencing on drug resistance. RESULTS: The polyploid T-MDA-MB-231 cells grew in vitro continuously and maintained constant DNA content. They had a larger cell size, and grew more slowly than MDA-MB-231 cells. The IC(50(s)) of T-MDA-MB-231 cells were significantly higher than that of the MDA-MB-231 cells: paclitaxel: (6.37 ± 0.07) vs. (2.05 ± 0.83) µmol/L; docetaxel: (32.98 ± 1.48) vs. (11.95 ± 0.98) µmol/L; vincristine: (35.28 ± 1.66) vs. (14.58 ± 0.94) µmol/L; oxaliplatin: (19.07 ± 0.45) vs. (9.75 ± 1.05) µmol/L; 5-Fu: (85.49 ± 3.21) vs. (31.35 ± 1.51) µmol/L; and epirubicin: (0.53 ± 0.06) vs. (0.15 ± 0.01) µmol/L, (all P < 0.05). The IC(50(s)) of VP16 in T-MDA-MB-231 cells was (2.85 ± 0.50)µmol/L, significantly lower than the (12.20 ± 1.55) µmol/L in MDA-MB-231 cells (P < 0.05), and that of T-MDA-MB-231 cells after Bcl-2-knocked down by siRNA was (19.59 ± 0.48) µmol/L, significantly higher than the (12.20 ± 1.55) µmol/L in the MDA-MB-231 cells (P < 0.05). The IC(50(s)) of docetaxel of T-MDA-MB-231 cells after Bcl-2-knocked down by siRNA was (21.52 ± 0.68) µmol/L, significantly decreased and lower than that before Bcl-2 silencing (32.98 ± 1.48) µmol/L. CONCLUSIONS:
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Authors | Juan Hao, Bi-bo Yuan, Yuan-fu Xu, Juan Yu, Guo-yan Liu, De-hua Wang |
Journal | Zhonghua zhong liu za zhi [Chinese journal of oncology]
(Zhonghua Zhong Liu Za Zhi)
Vol. 34
Issue 6
Pg. 419-24
(Jun 2012)
ISSN: 0253-3766 [Print] China |
PMID | 22967442
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Antineoplastic Agents, Phytogenic
- Organoplatinum Compounds
- Proto-Oncogene Proteins c-bcl-2
- RNA, Messenger
- RNA, Small Interfering
- Taxoids
- Oxaliplatin
- Docetaxel
- Epirubicin
- Vincristine
- Etoposide
- Paclitaxel
- Nocodazole
- Fluorouracil
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Topics |
- Antineoplastic Agents
(pharmacology)
- Antineoplastic Agents, Phytogenic
(pharmacology)
- Apoptosis
(drug effects)
- Breast Neoplasms
(genetics, metabolism, pathology)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Docetaxel
- Down-Regulation
- Drug Resistance, Neoplasm
- Epirubicin
(pharmacology)
- Etoposide
(pharmacology)
- Female
- Fluorouracil
(pharmacology)
- Gene Knockdown Techniques
- Humans
- Inhibitory Concentration 50
- Nocodazole
(pharmacology)
- Organoplatinum Compounds
(pharmacology)
- Oxaliplatin
- Paclitaxel
(pharmacology)
- Polyploidy
- Proto-Oncogene Proteins c-bcl-2
(genetics, metabolism)
- RNA, Messenger
(metabolism)
- RNA, Small Interfering
(genetics)
- Taxoids
(pharmacology)
- Vincristine
(pharmacology)
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