Background
The dilemma of pancreatic cancer treatment has become a global challenge. For this reason, effective, feasible, and new medical methods are currently much-needed. Betulinic acid (BA) has been valued as a potential therapy for pancreatic cancer. However, the mechanism by which BA exerts an inhibitory effect on the development of pancreatic cancer remains elusive.
Methods
A rat model and two cell models of pancreatic cancer were established, and the effect of BA on pancreatic cancer was verified
in vivo
and
in vitro
by using MTT, Transwell, flow cytometry, RT-PCR, Elisa and immunohistochemistry. At the same time, miR-365 inhibitors were introduced to test whether BA played a role in mediating miR-365.
Results
BA can significantly inhibit the proliferation and invasion of pancreatic cancer cells and promote apoptosis.
In vivo
experiments, BA can significantly lower the number of cancer cells and tumor volume in the rat model of pancreatic cancer.
In vitro
, it was found that BA inhibited the protein level and phosphorylation level of AKT/STAT3 by mediating the expression of miR365/BTG2/IL-6. Like BA, miR-365 inhibitors also significantly inhibited cell viability and invasion ability, and inhibited the protein level and phosphorylation level of AKT/STAT3 by changing the expression of BTG2/IL-6, and their combination had a synergistic effect.
Conclusion
BA inhibits AKT/STAT3 expression and phosphorylation by modulating miR-365/BTG2/IL-6 expression, and BA inhibits the progression of pancreatic cancer through the aforementioned mechanism.
a little more noticeable tendency in NPS group. AI increase was relatively higher in early, NPS, high dose groups (pZ0.076). The recovery tendency in late phase (14 weeks) was a little bit more in pancreatic shield (PS), high dose group (pZ0.067). Crypt atrophy was determined by the ratio of area occupied by connective tissue in mucosa. This tended to be high in low dose, NPS group (pZ0.062). It also showed an increasing trend in late phase especially in PS group (pZ0.032 in low dose group) (pZ0.012 in high dose group). IL-6 reflected the change with radiation dose escalation (pZ0.020). HIF-1a (pZ0.002 in low dose group, pZ0.001 in high dose group), NF-kB (pZ0.003 in low dose group, pZ0.038 in high dose group), and VEGF (pZ0.016 in low dose group, pZ0.006 in high dose group) were generally associated with tissue recovery at late phase. Conclusion: CDIA technique may provide the proper irradiation method free from volume effect deviation. Radiation-induced GIT toxicity was related to dose escalation with differential recovery over time. PS seems to be advantageous in terms of toxicity inhibition compared to NPS. These results can be a theoretical basis for reducing the radiation toxicity by confirming the relationship between the local irradiation and multi-organic impact with future studies.
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