For their study, the team chose to culture and harvest the cells of triple negative breast cancer (TNBC) cell line, HCC1937. In their study, published in the Journal of Traditional Chinese Medicine, they explained that TNBC is an incredibly progressive, highly invasive breast cancer subtype with a poor prognosis.. This made it ideal for their work.
Once the cells were readied into a single-cell suspension, they were divided into numerous experimental groups. The groups consisted of a blank group, a control group, and groups that were administered varying dosages of tetrandrine or arsenic trioxide. Following this, the cells were incubated, treated with dimethyl sulfoxide, oscillated, then measured. These steps were repeated two more times.
The researchers made use of the median-effect principle to assess the inhibition rate of the substances. Tetrandrine concentrations at 1.73 microgram/mL (μg/mL) resulted in a HC1937 cell inhibition rate of 21.3 percent. Arsenic trioxide concentrations of 2.75 μg/mL yielded an inhibition rate of 33.4 percent. These results were noted as being indicative of the efficacy of the substances as a combination rather than as monotherapies.
However, further evaluation showed that this only applied to specific concentrations. A combination index (CI) of less than one resulted in a weak synergy. By contrast, a (CI) that was greater than one led to the drugs generating “antagonistic effects." The best CI was found to be approximately equal to one, or when the tumor inhibition rate was equivalent to 0.5. This combination was utilized in all succeeding experiments.
Through real-time polymerase chain reaction (PCR) analysis and western blotting, the researchers discovered that the mixture of tetrandrine and arsenic trioxide could upregulate caspase-3 in HCC1937 cells. This protease is often called the “death protease” due to its role in apoptosis, the process of programmed cell death that cancer cells avoid. Caspase-3 is usually dormant within the cytoplasm. But the administration of the combination therapy enhanced its activity by a significant margin. (Related: Do You Know Your Leptin Levels? (And Why You Should If You Want to Prevent Breast Cancer))
Additionally, the tetrandrine plus arsenic trioxide combination was also found to impact the expression of Bid, Bax, Bcl-2, and survivin genes. All four of these genes are related to apoptosis. However, Bid and Bax are pro-apoptotic genes, whereas Bcl-2 and survivin are anti-apoptotic genes. The expression of Bid and Bax genes was enhanced, and Bcl-2 and survivin were suppressed.
"In conclusion, our findings suggested that [tetrandrine] plus [arsenic trioxide] could synergistically induce apoptosis in HCC1937 cells, with potentially significant implications for treating breast cancer," wrote the researchers.
Although the results have been promising thus far, the researchers noted that the precise mechanisms behind them are still unknown. The data on the expression of apoptotic genes somewhat conflicted with the synergistic effects of the combination therapy. As such, more research into other probable mechanisms and targets would be necessary for future studies.
What are mutual promotion and mutual restraint?
An easy way to understand these two concepts is in the concept of the five elements: fire, earth, metal, water, and wood. Mutual promotion occurs when one element influences the generation of another, such as when wood produces fire. Mutual restraint is when one element controls the other, like how water restricts fire. Mutual promotion and mutual restraint are integral to one another. Promotion is key to growth and development. Restraint safeguards against the harm brought on by the excess of development.
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