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[A study on the effect of Tanshinone II A against human breast cancer in vivo]
Xin Zhang1, Pu-Rong Zhang, Jie Chen
1Department of Thyroid and Breast Surgery, West China Hospital, Sichuan University, Chengdu 610041, China.
Objective:
To confirm Tanshinone II A's (Tan II A) anti-cancer activity on nude mice bearing human breast cancer cells with estrogen receptor (ER) positive and negative and to elucidate the mechanism of its activity in vivo.
Methods:
Established the animal model of nude mices bearing human breast cell, both ER positive MCF-7 and ER negative MDA-MB-231, each group was divided into 3 subgroups, respectively by intraperitoneal injection of Tan II A at a dose of 30 mg/kg 4 times/week, by gavage of Tamoxifen at a dose of 1 mg/kg 7 times/ week and by solvent control for 4 weeks. All animals were tested for anti-cancer activity including the weights and the volumes of the tumor, apoptosis index by flow cytometry and expression of p53, bcl-2, cerbB-2 by immunohistochemistry method after the treatment.
Results:
In MCF-7 group, there were a 33.64% tumor mass volume reduction and a 32.24% tumor mass weight reduction after Tan II A treatment; in MDA-MB-231 group, a 38.34% tumor mass volume reduction and a 39.82% tumor mass weight reduction were observed in Tan II A subgroups; the differences between Tan II A and Tamoxifen or solvent control were statistically significant in both groups (P < 0.05); increase of apoptosic fiction by flow cytometry examination in Tan II A subgroups in both MCF-7 (48.31% +/- 5.84%) and MDA-MB-231(50.25% +/- 5.03%) groups were observed, there were both significant differences between Tan II A and the other subgroups (P < 0.05). Statistically significant decrease of p53 and bcl-2 expression were observed in Tan lI A between solvent control subgroup in both MCF-7 and MDA-MB-231 groups (P < 0.05) while cerbB-2 had no significant difference with control group (P > 0.05).
Conclusion:
Tan lI A can inhibit both breast cancer cell MCF-7 and MDA-MB-231 growth in vivo, which had better anti-cancer effect than Tamoxifen. The mechanism may be associated with the induction of apoptosis, down regulation of the expression level of gene bcl-2 and p53, but may not with the expression level of cerbB-2.
Insights
Tanshinone II A demonstrates significant anti-cancer effects against human breast cancer cells in vivo, outperforming Tamoxifen. Its mechanism involves inducing apoptosis and down-regulating p53 and bcl-2 gene expression.
Area of Science:
- Pharmacology
- Oncology
- Molecular Biology
Background:
- Breast cancer remains a leading cause of cancer-related deaths globally.
- Estrogen receptor (ER) status (positive or negative) influences treatment strategies for breast cancer.
- Tanshinone II A (Tan II A) is a compound with potential anti-cancer properties that warrants further investigation.
Purpose of the Study:
- To evaluate the anti-cancer efficacy of Tanshinone II A (Tan II A) in a nude mouse model bearing human breast cancer cells.
- To compare the effects of Tan II A with Tamoxifen, a standard breast cancer treatment.
- To elucidate the in vivo molecular mechanisms underlying Tan II A's anti-cancer activity.
Main Methods:
- Establishment of a nude mouse model with human ER-positive (MCF-7) and ER-negative (MDA-MB-231) breast cancer cells.
- Treatment groups included intraperitoneal injection of Tan II A, oral gavage of Tamoxifen, and solvent control over four weeks.
- Assessment of anti-cancer activity involved tumor weight/volume measurements, flow cytometry for apoptosis, and immunohistochemistry for p53, bcl-2, and cerbB-2 expression.
Main Results:
- Tan II A significantly reduced tumor volume and weight in both MCF-7 (33.64% volume, 32.24% weight) and MDA-MB-231 (38.34% volume, 39.82% weight) models compared to controls (P < 0.05).
- Tan II A treatment led to a significant increase in apoptosis in both cell lines (MCF-7: 48.31%, MDA-MB-231: 50.25%; P < 0.05).
- Significant down-regulation of p53 and bcl-2 expression was observed with Tan II A treatment, while cerbB-2 expression showed no significant difference.
Conclusions:
- Tanshinone II A effectively inhibits the growth of both ER-positive and ER-negative human breast cancer cells in vivo.
- Tan II A exhibits superior anti-cancer effects compared to Tamoxifen in this model.
- The anti-cancer mechanism of Tan II A is associated with apoptosis induction and down-regulation of p53 and bcl-2, but not cerbB-2.