Metformin and aspirin, the new uses of these two centuries-old medicines, will be brought out from time to time by the singularity cakes. Everyone likes to see things like for old medicines and new , let alone during the new crown pneumonia epidemic, similar studies have sprung up.
squeezed his fingers and settled, it seems that the monthly praise of metformin has been praised? Let's talk about aspirin that hasn't been seen for a while. A recent study by an Indian research team found that aspirin can help chemotherapy drugs effectively kill cancer stem cells (CSCs) , which is a headache in cancer treatment.
aspirin can increase the expression of SMAR1 gene in breast cancer cells, and SMAR1 can inhibit the formation of cancer stem cell drug efflux pump. If chemotherapeutic drugs cannot be effluxed, cancer stem cells are more likely to be killed by chemotherapy, thereby enhancing the effect of commonly used chemotherapeutics [1]. The research was published on Science Signaling.
I saw the whole research process in one picture, and praised the scientist who made the picture.
(picture source: Bose Institute)
Singularity Cake once heard a big domestic coffee say, "Various cancer treatment drugs that can't kill cancer stem cells, Neither can be regarded as a radical cure, which is the same as the cccDNA of hepatitis B." Cancer stem cells can play an important role in the occurrence and development of cancer, but the most annoying thing is their drug resistance.
Many people may think of various primary or secondary gene mutations when they hear about drug resistance, but in fact, there are many mutation-independent mechanisms for drug resistance in cancer stem cells [2], the most typical being drug efflux Pump. Chemotherapy drugs cannot stay in cancer cells, and of course they can't kill.
The initial research direction of Indian researchers did not center on aspirin, but started from the tumor suppressor gene SMAR1. Increasing the expression of SMAR1 gene in breast cancer can enhance the lethality of chemotherapy drugs [3], against cancer stem cells, can SMAR1 continue to help chemotherapy drugs to relieve drug resistance? The
research team first analyzed the SMAR1 gene expression in more than 2000 breast cancer patients, and found that the higher expression of SMAR1 was related to the longer recurrence-free survival (RFS) of the patients (HR=0.72), but in stage III breast cancer , The expression of SMAR1 in patient tumor samples will be significantly less than that of stage II breast cancer.
HR=0.72, the clinical significance is more obvious.
That is to say, the more advanced the patient's cancer, the more tumor stem cells in the tumor, the less the expression of SMAR1 may be. The results directly verified by the research team in animal experiments also showed that the expression of SMAR1 in cancer stem cells is indeed significantly reduced, which seems to be "I do not have him" with cancer stem cells. Further experiments by
showed that the SMAR1 protein can bind to the promoter of the ABCG2 gene, and recruit histone deacetylase-2 (HDAC2) to inhibit the transcription of the ABCG2 gene, resulting in a significant reduction in the protein encoded by it. And this ABCG2 is an important drug efflux pump for cancer stem cells.
Without the efflux pump, cancer stem cells can hardly resist aggressive chemotherapy drugs. However, the research team found that the two important stem cell factors in cancer stem cells, Oct4 and Sox2, would in turn bind to the promoter of the SMAR1 gene in a similar manner, thereby inhibiting the effect of SMAR1 in turn.
At this time, the protagonist aspirin finally came out, because the Oct4 and Sox2 used in the countermeasures of tumor stem cells are exactly the sites that aspirin can inhibit [3]. Once aspirin is used, the expression level of SMAR1 is rapidly increased, thereby restoring the inhibitory effect on the efflux pump of cancer stem cells. The
research team is still youngIn the mouse model, the efficacy of aspirin combined with chemotherapeutics on breast cancer was verified: the picture below shows that the effect of aspirin alone is not obvious, but the combination of the commonly used chemotherapy drug doxorubicin (Dox) reduces The tumor effect is really visible to the naked eye. It can be said that aspirin + doxorubicin reduced tumors by nearly 90%. Tanya Das, the corresponding author of the
paper, said that the anti-cancer effect of aspirin combined with chemotherapeutics can not only be solved by this study, but also by promoting Apoptosis of cancer stem cells plays a role [4]. Moreover, this research team has previously found that aspirin can inhibit the metastasis of cancer stem cells in lung cancer models [5].
has such a multi-layered effect at the same time. If you don't verify the therapeutic value of aspirin in the clinic, it will definitely not work. At present, there have been a number of clinical trials in the United States that use aspirin, combined with chemotherapy, surgery, radiotherapy and even immunotherapy to fight cancer, and the results are really worth looking forward to. The development of the
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References:
1.Bhattacharya A, Mukherjee S, Khan P, et al. SMAR1 repression by pluripotency factors and consequent chemoresistance in breast cancer stem-like cells is reversed by aspirin [J]. Science Signaling, 2020, 13(654) : eaay6077.
2.Marine JC, Dawson SJ, Dawson M A. Non-genetic mechanisms of therapeutic resistance in cancer [J]. Nature Reviews Cancer, 2020.
3.Chen J, Xu R, Xia J, et al. Aspirin inhibits hypoxia-mediated lung cancer cell stemness and exosome function[J]. Pathology-Research and Practice, 2019, 215(6): 152379.
4.Saha S, Mukherjee S, Khan P, et al. Aspirin suppresses the acquisition of chemoresistance in breast cancer by disrupting an NFκB–IL6 signaling axis responsible for the generation of cancer stem cells[J]. Cancer Research, 2016, 76(7): 2000-2012.
5.Khan P, Bhattacharya A, Sengupta D, et al. Aspirin enhances cisplatin sensitivity of resistant non-small cell lung carcinoma stem-like cells by targeting mTOR-Akt axis to repress migration[J]. Scientific Reports, 2019, 9(1): 1-15.
Source of head picture: Pixabay Author | 谭硕
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