Mechanistic of Artemisinin Extracts Modulating Cisplatin Resistance in Lung Cancer A549/DDP Cells via the PI3K/Akt Pathway

Weiwei Zeng and Lei Xia

Background and Objective: Dihydroartemisinin (DHA) is the principal metabolite of artemisinin, derived from the herb Artemisia annua and is known for its efficacy in controlling various forms of malaria and exhibiting enhanced antitumor activity. This work was to demonstrate mechanisms of DHA on proliferation (Pro), apoptosis (Apo) and cisplatin (DDP) resistance in LC A549/DDP cells through PI3K/Akt signaling. Materials and Methods: The DHA solid dispersion (DHA-SD) was prepared employing a solvent methodology and its characterization was analyzed. Subsequently, the pharmacokinetic characteristics and bioavailability of DHA-SD were assessed in rats. Human lung adenocarcinoma DDP-resistant cells A549/DDP in the logarithmic growth phase were rolled into Ctrl group, DDP group, DHA group, DHA-SD group, DDP+DHA group and DDP+DHA-SD group. Cell Pro inhibition was measured employing MTT assay, while flow cytometry was employed to assess cell Apo rates. Western blot analysis was performed to evaluate the protein ELs of Caspase-3, Cleaved Caspase-3, Bax, Bcl-2, p-PI3K and p-Akt. Results: The DHA-SD possessed similar structures and characteristics to the original DHA. Compared with the Ctrl group, the Pro inhibition rate and Apo rate of the DDP group were significantly increased (p<0.05); compared with the DDP group, the Pro inhibition rate and Apo rate were significantly increased and the protein expression of Caspase-3, Cleaved Caspase-3 and Bax were significantly increased and the protein expressions of Bcl-2, p-PI3K and p-Akt were significantly decreased in DHA group, DHA-SD group, DDP+DHA group and DDP+DHA-SD group (p<0.05). Among them, the DDP+DHA-SD group had the most obvious changes in cell indexes (p<0.05). Conclusion: The DHA-SD markedly enhanced the bioavailability of DHA. The combination of DHA and DHA-SD with DDP can inhibit the Pro of LC A549/DDP cells, induce cell Apo and reverse DDP resistance and these effects were associated with the PI3K/Akt signaling.

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