Abstract：
OBJECTIVE: Lipids are essential for energy production, signaling, and membrane formation, hence increased lipid metabolism may lead to cancer growth. 4-cholesten-3-one (4Cone), a sterol metabolite, has various biological activities, including the inhibition of cancer growth. This study examined whether 4Cone could change the lipid profile of triple-negative breast cancer cells (MDA-MB-231) and whether in combination with the anti-cancer chemotherapy docetaxel (TXT) could further reduce cancer aggressiveness.
METHODS: The effect of 4Cone, TXT, or their combination (4Cone/TXT) on migration and proliferation was examined utilizing the wound healing and MTT assays. The expression of the lipogenesis-related enzymes was assessed using RT-qPCR and lipid profile was examined using mass spectrometry.
RESULTS: 4Cone and TXT individually reduced cell viability and migration of MDA-MB-231 cancer cells; however, their combination (4Cone/TXT) had a greater impact on both attributes. All treated cells showed markedly decreased levels of the multidrug resistance enzyme PGP as well as the lipogenic enzymes FASN, ACC1, SCD1, HMGCR, and DGAT. Furthermore, lipid fingerprints were markedly different in treated cells compared with the untreated group. 4Cone increased the percentage of sphingomyelin (SM) while it decreased the percentage of ceramide (Cer); 4Cone in conjunction with TXT had the reverse effect. Triglyceride levels were reduced in 4Cone- and 4Cone/TXT-treated cells, but interestingly, they increased in TXT-treated cells. Additionally, treated cancer cells exhibited changes in glycerophospholipid subclasses.
CONCLUSIONS: 4Cone alone or in combination with TXT alters the lipid profile by reducing a key lipogenic enzyme, resulting in the inhibition of cell proliferation and migration.
METHODS: The effect of 4Cone, TXT, or their combination (4Cone/TXT) on migration and proliferation was examined utilizing the wound healing and MTT assays. The expression of the lipogenesis-related enzymes was assessed using RT-qPCR and lipid profile was examined using mass spectrometry.
RESULTS: 4Cone and TXT individually reduced cell viability and migration of MDA-MB-231 cancer cells; however, their combination (4Cone/TXT) had a greater impact on both attributes. All treated cells showed markedly decreased levels of the multidrug resistance enzyme PGP as well as the lipogenic enzymes FASN, ACC1, SCD1, HMGCR, and DGAT. Furthermore, lipid fingerprints were markedly different in treated cells compared with the untreated group. 4Cone increased the percentage of sphingomyelin (SM) while it decreased the percentage of ceramide (Cer); 4Cone in conjunction with TXT had the reverse effect. Triglyceride levels were reduced in 4Cone- and 4Cone/TXT-treated cells, but interestingly, they increased in TXT-treated cells. Additionally, treated cancer cells exhibited changes in glycerophospholipid subclasses.
CONCLUSIONS: 4Cone alone or in combination with TXT alters the lipid profile by reducing a key lipogenic enzyme, resulting in the inhibition of cell proliferation and migration.
摘要：
目的：脂质对能量生产至关重要，信令,和膜的形成，因此，脂质代谢增加可能导致癌症生长。4-cholesten-3-one（4Cone），甾醇代谢产物,具有各种生物活性，包括抑制癌症生长。这项研究检查了4Cone是否可以改变三阴性乳腺癌细胞（MDA-MB-231）的脂质分布，以及与多西他赛（TXT）联合使用是否可以进一步降低癌症侵袭性。
方法：4Cone的效果，TXT,或其组合(4Cone/TXT)对迁移和增殖的使用创伤愈合和MTT测定进行检查。使用RT-qPCR评估脂肪生成相关酶的表达,并使用质谱法检查脂质谱。
结果：4Cone和TXT分别降低MDA-MB-231癌细胞的细胞活力和迁移；然而，它们的组合(4Cone/TXT)对这两个属性都有更大的影响。所有处理的细胞显示多药耐药酶PGP以及脂肪生成酶FASN的水平显著降低,ACC1,SCD1,HMGCR,还有DGAT.此外，与未处理组相比，处理细胞的脂质指纹图谱明显不同。4Cone增加了鞘磷脂（SM）的百分比，而降低了神经酰胺（Cer）的百分比；4Cone与TXT结合具有相反的作用。在4Con和4Cone/TXT处理的细胞中甘油三酯水平降低,但有趣的是,它们在TXT处理的细胞中增加。此外,治疗的癌细胞表现出甘油磷脂亚类的变化。
结论：4Cone单独或与TXT联合使用通过减少关键的脂肪生成酶来改变血脂谱，导致细胞增殖和迁移的抑制。
方法：4Cone的效果，TXT,或其组合(4Cone/TXT)对迁移和增殖的使用创伤愈合和MTT测定进行检查。使用RT-qPCR评估脂肪生成相关酶的表达,并使用质谱法检查脂质谱。
结果：4Cone和TXT分别降低MDA-MB-231癌细胞的细胞活力和迁移；然而，它们的组合(4Cone/TXT)对这两个属性都有更大的影响。所有处理的细胞显示多药耐药酶PGP以及脂肪生成酶FASN的水平显著降低,ACC1,SCD1,HMGCR,还有DGAT.此外，与未处理组相比，处理细胞的脂质指纹图谱明显不同。4Cone增加了鞘磷脂（SM）的百分比，而降低了神经酰胺（Cer）的百分比；4Cone与TXT结合具有相反的作用。在4Con和4Cone/TXT处理的细胞中甘油三酯水平降低,但有趣的是,它们在TXT处理的细胞中增加。此外,治疗的癌细胞表现出甘油磷脂亚类的变化。
结论：4Cone单独或与TXT联合使用通过减少关键的脂肪生成酶来改变血脂谱，导致细胞增殖和迁移的抑制。
