Inspired by Ke et al 2021 and Shih et al.[1,2]
EA – electroacupuncture
key to acronyms
MM – multiple myeloma
LC-MS – liquid chromatography mass spectrometry
UHPLC-MS – ultra high performance LC-MS
MA – manual acupuncture
SR – systematic review
For the final blog of the year, I have a couple of recent papers where acupuncture has been used to augment antitumour effects or counteract adverse effects in cancer treatment. One is an experimental paper in mice with multiple myeloma and the other is an SR in patients with breast cancer.
I already highlighted a couple of papers on antitumour effects in a mouse model of breast cancer in March 2021: ST36 EA and antitumour effects. This time, rather than using EA in combination with a chemotherapeutic agent, it is combined with bortezomib, a proteasome inhibitor.
bortezomib – a proteasome inhibitor
Proteasomes are intracellular protein complexes that degrade unneeded, misfolded, or damaged proteins through proteolysis, that is breaking the bonds between peptides. The enzymes that aid this process are called proteases.
The precise therapeutic mechanism or mechanisms of bortezomib are not fully defined, but the boron atom it contains binds strongly to a catalytic site on the 26S proteasome, and hence inhibits breakdown of certain proteins. It is thought that by doing so some pro-apoptotic factors may be preserved in neoplastic cells, and hence the antitumour effect.
In the laboratory study by Ke et al, EA or bortezomib or a combination was applied to a mouse model of MM and compared with the model without treatment as a control. Eight to 10 animals were used in each group. The EA was applied 3 times a week at 2/100Hz and 2mA to LI4 and ST36.
The main outcome was survival, but the point of the study was to examine differences in serum metabolites using LC-MS and UHPLC-MS. The median survival time of the model was 47 days. This was increased in the EA group to 67 days, in the bortezomib group to 73.5 days, and in the combined group to 79 days. In human terms that equates to about 12 years extra lifespan, according to my calculations using data from a paper in the journal Life Sciences titled ‘Men and mice: Relating their ages’.[3] For EA alone the median increased lifespan of 20 days equates to nearly 8 years. That alone is quite impressive.
In the mouse model of MM:
bortezomib plus EA increased median lifespan by 68%
bortezomib alone increased median lifespan by 56%
EA alone increased median lifespan by 43%
The rather complex metabolomic analysis revealed that the metabolites ornithine and arginine were significantly decreased in the serum of the combined group compared with that of the control group. Arginine was shown to promote cell growth in several tumour cell lines and high expression of the gene for ornithine decarboxylase was associated with poor overall survival.
The second paper I am highlighting is an SR on acupuncture for chemotherapy-induced leukopenia in patients with breast cancer. I think this is the first review I have come across on this topic and it includes 9 studies from China and one pilot study from Australia with a total of 650 women. The interventions were rather heterogeneous with four using moxibustion alone, 2 applying catgut embedding to acupuncture points, 2 using EA and the remaining 2 applying MA. My favourite point (ST36) was used in 8 out of 10 protocols.
acupuncture for chemotherapy-induced leukopenia
It is reported as a positive review but of course most trials had a high RoB. The authors reported one trial with low RoB in every category, so I chose this one to check up on.[4] It was a trial of moxibustion with no description of blinding or sham control, and of the 64 different outcomes reported only 2 appear to be significantly in favour of the intervention group. At this point I regret highlighting the SR but I guess it is a reminder that a lot of published research conclusions cannot be taken at face value, and the author pays model for publishing has certain unhelpful incentives in this regard.
Not wanting to end my blogging year on such a negative note, there was certainly a tendency for the ‘acupuncture’ treated patients to be in a better position in terms of their white blood cells. So, if nothing else, this SR certainly leaves wide open the possibility for more rigorous testing of the hypothesis that acupuncture approaches might ameliorate chemotherapy-induced myelosuppression.
References
1 Ke M, Qian J, Hao F, et al. Acupuncture Synergized With Bortezomib Improves Survival of Multiple Myeloma Mice via Decreasing Metabolic Ornithine. Front Oncol 2021;11. doi:10.3389/fonc.2021.779562
2 Shih YW, Su JY, Kung YS, et al. Effectiveness of Acupuncture in Relieving Chemotherapy-induced Leukopenia in Patients With Breast Cancer: A Systematic Review With A Meta-Analysis and Trial Sequential Analysis. Integr Cancer Ther 2021;20. doi:10.1177/15347354211063884
3 Dutta S, Sengupta P. Men and mice: Relating their ages. Life Sci 2016;152:244–8. doi:10.1016/j.lfs.2015.10.025
4 Ji Y, Li S, Zhang X, et al. The Efficacy of Moxibustion for Breast Cancer Patients with Chemotherapy-Induced Myelosuppression during Adjuvant Chemotherapy: A Randomized Controlled Study. Evid Based Complement Alternat Med Published Online First: 2021. doi:10.1155/2021/1347342
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