曲妥珠单抗 (TRZ) 是一种治疗人表皮生长因子受体 2 (HER2) 乳腺癌亚型 (HER2 BC) 的药物，长期使用会诱发耐药性。冰片（BOR）对多种癌症具有抗癌作用。然而，其对 HER2 BC 的抗癌作用仍不清楚。本研究旨在确定 BOR 的潜在靶基因及其对克服 HER2 BC 对 TRZ 耐药性的影响。通过生物信息学方法确定了 BOR 对 HER2 BC 细胞的潜在靶标的枢纽基因。通过TRZ反复诱导HCC1954癌细胞获得耐药HCC1954细胞（HCC1954-TR）。然后对细胞进行涉及单一化合物及其组合的细胞毒性测试。然后，使用定量逆转录聚合酶链反应测定中心基因表达。通过分子对接测量BOR与选定蛋白质之间的相互作用。通过生物信息学方法获得Hub基因IL6、TNF、ESR1、IL1B、CYP19A1、AR、NR3C1、RELA、CYP17A1和GPT。 HCC1954-TR细胞建立成功。与单独使用 BOR 或 TRZ 相比，亲本 HCC1954（400 µg/mL 和 25 µM）和 HCC1954-TR（800 µg/mL 和 100 µM）的 TRZ-BOR 组合治疗产生了明显更好的结果。 TRZ-BOR组合下AR、GPT和ESR1的表达与单次暴露相比有显着差异。 CYP19A1、CYP17A1、NR3C1 和 IL-1β 的分子对接研究强调了 BOR 与此类蛋白之间的潜在相互作用。BOR 改善了 TRZ 对 HCC1954 和 HCC1954-TR 细胞系的细胞毒作用，其中它专门针对 AR、ESR1 和GPT 基因。此外，BOR效应抵消了HCC1954-TR细胞对TRZ的耐药性，是由基因CYP19A1、CYP17A1、NR3C1、IL-1和RELA介导的。然而，还需要进一步的研究来验证它们在 BOR 活性中的作用，以规避 HER2 BC 对 TRZ 的耐药性。

The long-term use of trastuzumab (TRZ), a therapeutic agent for human epidermal growth factor receptor 2 (HER2)+ breast cancer subtype (HER2+ BC), induces resistance. Borneol (BOR) exerts anticancer effects on various types of cancer. However, its anticancer effect on HER2+ BC remains unknown. This study aimed to determine the potential target genes of BOR and its effect on overcoming the resistance of HER2+ BC to TRZ.The hub gene of  BOR's potential target on HER2+ BC cells was determined via a bioinformatics approach. Resistant HCC1954 cells (HCC1954-TR) were obtained through repeated inducement of HCC1954 cancer cells with TRZ. The cells were then subjected to cytotoxic tests involving single compounds and their combinations. Then, the hub gene expression was determined using quantitative reverse-transcription polymerase chain reaction. The interaction between BOR and selected proteins was measured through molecular docking.Hub genes IL6, TNF, ESR1, IL1B, CYP19A1, AR, NR3C1, RELA, CYP17A1, and GPT were obtained via a bioinformatics approach. HCC1954-TR cells were successfully established. The TRZ-BOR combination treatment of parental HCC1954 (400 µg/mL and 25 µM) and HCC1954-TR (800 µg/mL and 100 µM) yielded considerably better results compared with BOR or TRZ alone. The expressions of AR, GPT, and ESR1 under the TRZ-BOR combination were notably different compared with those under single exposure. The molecular docking study of CYP19A1, CYP17A1, NR3C1, and IL-1β highlighted the potential interaction between BOR and such proteins.BOR improved the cytotoxic effects of TRZ on HCC1954 and HCC1954-TR cell lines, where it specifically targets AR, ESR1, and GPT genes. In addition, the BOR effect, which counteracted the resistance of HCC1954-TR cells to TRZ, was mediated by genes CYP19A1, CYP17A1, NR3C1, IL-1, and RELA. However, additional research is required to validate their role in BOR activity to circumvent the resistance of HER2+ BC to TRZ.