HSP90AB1 as the Druggable Target of Maggot Extract Reverses Cisplatin Resistance in Ovarian Cancer

Abstract

Cisplatin resistance is a crucial factor affecting ovarian cancer patient’s survival rate, but the primary mechanism underlying cisplatin resistance in ovarian cancer remains unclear, and this prevents the optimal use of cisplatin therapy. Maggot extract (ME) is used in traditional Chinese medicine for patients with comas and patients with gastric cancer when combined with other drug treatments. In this study, we investigated whether ME enhances the sensitivity of ovarian cancer cells to cisplatin. Two ovarian cancer cells—A2780/CDDP and SKOV3/CDDP—were treated with cisplatin and ME in vitro. SKOV3/CDDP cells that stably expressed luciferase were subcutaneously or intraperitoneally injected into BALB/c nude mice to establish a xenograft model, and this was followed by ME/cisplatin treatment. In the presence of cisplatin, ME treatment effectively suppressed the growth and metastasis of cisplatin-resistant ovarian cancer in vivo and in vitro. RNA-sequencing data showed that HSP90AB1 and IGF1R were markedly increased in A2780/CDDP cells. ME treatment markedly decreased the expression of HSP90AB1 and IGF1R, thereby increasing the expression of the proapoptotic proteins p-p53, BAX, and p-H2AX, while the opposite effects were observed for the antiapoptotic protein BCL2. Inhibition of HSP90 ATPase was more beneficial against ovarian cancer in the presence of ME treatment. In turn, HSP90AB1 overexpression effectively inhibited the effect of ME in promoting the increased expression of apoptotic proteins and DNA damage response proteins in SKOV3/CDDP cells. Inhibition of cisplatin-induced apoptosis and DNA damage by HSP90AB1 overexpression confers chemoresistance in ovarian cancer. ME can enhance the sensitivity of ovarian cancer cells to cisplatin toxicity by inhibiting HSP90AB1/IGF1R interactions, and this might represent a novel target for overcoming cisplatin resistance in ovarian cancer chemotherapy.

Large-Scale Identification of Lysine Crotonylation Reveals Its Potential Role in Oral Squamous Cell Carcinoma

“… 44 In ovarian cancer, targeting HSP90AB1 has emerged as a viable strategy, as its inhibition can reverse cisplatin resistance and impede tumor growth. 45 Collectively, these investigations underscore the multifaceted role of HSP90AB1 in cancer biology, exerting influence on diverse cellular processes and pathways that contribute to tumor development and progression. Further exploration of HSP90AB1 and its interactions with client proteins holds promise for the development of targeted therapies in cancer treatment.…”

Research Progress on New Functions of Animal and Plant Proteins

“…In addition, the HSP90AB1 gene associated with ovarian cancer is a member of the 90 family of heat shock proteins involved in signal transduction, protein folding and degradation, and morphological evolution [57]. HSP90AB1 overexpression has been found to play an important role in cisplatin resistance in ovarian cancer, and maggot extracts (the larvae of Lucilia sericata) can enhance the sensitivity of ovarian cancer cells to cisplatin toxicity by reducing HSP90AB1 expression and increasing cisplatin-induced DNA damage [58]. It can be seen that protein raw materials may play a certain role in the adjuvant treatment of ovarian cancer.…”