Combination of porous Se@SiO2 nanospheres and docetaxel exhibits anti-castration-resistant prostate cancer activity by downregulating ATG14-dependent autophagy

IF 13.2 1区 材料科学 Q1 CHEMISTRY, MULTIDISCIPLINARY Nano Today Pub Date : 2024-09-16 DOI:10.1016/j.nantod.2024.102499
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Abstract

Chemotherapy remains the core anticancer treatment for castration-resistant prostate cancer (CRPC). However, drug resistance still poses a major obstacle, leading to shorter survival times. Given the biosafety of porous Se@SiO2 nanospheres in normal tissues, their combination with chemotherapeutic drugs has emerged as an effective treatment for cancer. It is unknown whether porous Se@SiO2 nanospheres can protect CRPC cells from drug resistance. In our study, we synthesized porous Se@SiO2 nanospheres and confirmed their characteristics in line with previous studies. We discovered that porous Se@SiO2 nanospheres sensitize CRPC to docetaxel (DTX) treatment, both in vitro and in vivo. Mechanistically, the nanospheres induce dephosphorylation of autophagy-related 14 (ATG14) at Y357 by upregulating the expression of the cellular form of prostatic acid phosphatase (cPAP) protein, which prevents the induction of autophagy and the survival of prostate cancer cells after DTX treatment. Furthermore, there is a negative correlation between cPAP and autophagy in CRPC. Our results suggest that the combination of porous Se@SiO2 nanospheres with DTX could be a potentially effective treatment for CRPC.

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多孔Se@SiO2纳米球与多西他赛的组合通过下调ATG14依赖性自噬作用显示出抗前列腺癌的活性
化疗仍是治疗耐受性前列腺癌(CRPC)的核心抗癌疗法。然而,耐药性仍然是一个主要障碍,导致生存时间缩短。鉴于多孔 Se@SiO2 纳米球在正常组织中的生物安全性,它们与化疗药物的结合已成为一种有效的癌症治疗方法。多孔Se@SiO2纳米球能否保护CRPC细胞免受耐药性的影响尚不清楚。在我们的研究中,我们合成了多孔 Se@SiO2 纳米球,并证实其特性与之前的研究一致。我们发现多孔Se@SiO2纳米球在体外和体内都能使CRPC对多西他赛(DTX)治疗敏感。从机理上讲,纳米球通过上调前列腺酸性磷酸酶(cPAP)蛋白细胞形式的表达,诱导自噬相关14(ATG14)在Y357处去磷酸化,从而阻止了自噬的诱导和DTX治疗后前列腺癌细胞的存活。此外,在 CRPC 中,cPAP 与自噬之间存在负相关。我们的研究结果表明,多孔Se@SiO2纳米球与DTX的结合可能是治疗CRPC的一种有效方法。
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来源期刊
Nano Today
Nano Today 工程技术-材料科学:综合
CiteScore
21.50
自引率
3.40%
发文量
305
审稿时长
40 days
期刊介绍: Nano Today is a journal dedicated to publishing influential and innovative work in the field of nanoscience and technology. It covers a wide range of subject areas including biomaterials, materials chemistry, materials science, chemistry, bioengineering, biochemistry, genetics and molecular biology, engineering, and nanotechnology. The journal considers articles that inform readers about the latest research, breakthroughs, and topical issues in these fields. It provides comprehensive coverage through a mixture of peer-reviewed articles, research news, and information on key developments. Nano Today is abstracted and indexed in Science Citation Index, Ei Compendex, Embase, Scopus, and INSPEC.
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