Sains Malaysiana 50(5)(2021): 1393-1405

http://doi.org/10.17576/jsm-2021-5005-18

 

Anti-Tumor Activity of Metformin in Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer Cells

(Aktiviti Anti-Tumor Metformin pada Reseptor Faktor Pertumbuhan Epidermis Manusia 2 Positif Sel Kanser Payudara)

 

FATHUL HUDA1,2*, SARI EKAWATI3, ANINDY PUTRI ADDINA3, AHMAD FARIED2,4, AFIAT BERBUDI1,2, TAOFIK RUSDIANA5, TENNY PUTRI6, NURUL QOMARILLA6, LUKMAN HILFI7, IWAN SETIAWAN1 & MUHAMMAD HASAN BASHARI1,2

 

1Department of Biomedical Science, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161, Indonesia

 

2Oncology and Stem Cell Working Group, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161, Indonesia

 

3Bachelor of Medicine Program, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161, Indonesia

 

4Department of Neurosurgery, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161, Indonesia

 

5Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Universitas Padjadjaran, Bandung 40161, Indonesia

 

6Cell Culture Laboratory, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161, Indonesia

 

7Department of Public Health, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161, Indonesia

 

Diserahkan: 18 Disember 2019/Diterima: 29 September 2020

 

ABSTRACT

Breast Cancer (BC) is the leading cause of cancer death in women. One BC subtype is very aggressive with amplification of human epidermal growth factor receptor 2 (HER2) protein. Although specific HER2+ targeting agents are available, most of HER2+ BC patients develop resistant to these agents. Recent studies show that metformin, is able to become anti-tumor in various cancer cells. This research aims to evaluate anti-tumor activities of metformin to HER2+ BC cells in both sensitive and resistant to trastuzumab. A series of assays were performed to evaluate metformin anti-tumor activities in HCC-1954 and SKBR-3 HER2+ BC cells. MTT assay was performed to evaluate cell death, and inhibitory concentration (IC50), while scratch assay was performed to assess inhibition of cell migration and clonogenic assay to assess cell proliferation. p<0.05 was considered to be significant. Metformin could suppress the number of HER2+ BC cells. Viability assay showed suppression of viable cells after metformin incubation of 60 and 600 µM compared to control, 30 and 90%, respectively. Surprisingly, IC50 of metformin was smaller in HER2+ BC HCC-1954 cells that resistant to trastuzumab compare to the sensitive one (SKBR-3). Both were below 1 µM, with R2 more than 0.95. Additionally, clonogenic assay showed less colony number and colony area with at least p < 0.05 in colony number and p < 0.01 in the area. In addition, metformin inhibited cell migration of HER2+ BC cells. Metformin shows a potency as anti-tumor by inducing cell death, inhibiting cell proliferation and cell migration of HER2+ BC cells.

 

Keywords: Breast Cancer; HER2+; metformin; Trastuzumab resistant

 

ABSTRAK

Kanser Payudara (BC) adalah penyebab utama kematian akibat barah pada wanita. Satu subjenis BC sangat agresif dengan penguatan protein reseptor 2 faktor pertumbuhan epidermis manusia (HER2). Walaupun agen sasaran HER2 + khusus ada, kebanyakan pesakit HER2 + BC mengalami ketahanan terhadap agen ini. Kajian terbaru menunjukkan bahawa metformin mampu menjadi anti-tumor pada pelbagai sel barah. Penyelidikan ini bertujuan untuk menilai aktiviti anti-tumor metformin kepada sel HER2 + BC dengan sensitif dan tahan terhadap trastuzumab. Satu siri ujian dilakukan untuk menilai aktiviti anti-tumor metformin pada sel HCC-1954 dan SKBR-3 HER2 + BC. Ujian MTT dilakukan untuk menilai kematian sel dan kepekatan penghambatan (IC50), sementara ujian awal dilakukan untuk menilai penghambatan penghijrahan sel dan pengujian klonogenik untuk menilai percambahan sel. p <0.05 dianggap signifikan. Metformin dapat menekan bilangan sel HER2 + BC. Ujian daya maju menunjukkan penekanan sel yang berdaya maju setelah inkubasi metformin 60 dan 600 µM berbanding kawalan, masing-masing 30 dan 90%. Anehnya, IC50 metformin lebih kecil pada sel HER2 + BC HCC-1954 yang tahan terhadap trastuzumab dibandingkan dengan sel sensitif (SKBR-3). Kedua-duanya berada di bawah 1 µM, dengan R2 lebih daripada 0.95. Selain itu, ujian klonogenik menunjukkan bilangan koloni dan kawasan koloni yang kurang dengan sekurang-kurangnya p <0.05 pada bilangan koloni dan p < 0.01 di kawasan koloni. Sebagai tambahan, metformin menghalang penghijrahan sel HER2 + BC sel. Metformin menunjukkan potensi sebagai anti-tumor dengan mendorong kematian sel, menghambat percambahan sel dan penghijrahan sel HER2+ sel BC.

 

Kata kunci: HER2 +; kanser payudara (BC); metformin, rintangan Trastuzumab

 

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*Pengarang untuk surat-menyurat; email: fathul@unpad.ac.id

 

 

 

 

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